Category Archives: Stem Cell Therapy

MINNEAPOLIS--(BUSINESS WIRE)--The Center for International Blood and Marrow Transplantation (CIBMTR), is delighted to announce that Owhofasa Agbedia, MD, MPH, has been selected to receive the ASH-CIBMTR-ASTCT Career Development Award. The award includes a stipend of $100,000 to conduct clinical or laboratory-based hematology research projects and to be mentored in person by faculty at the CIBMTRs two parent institutions.

The CIBMTR is a research collaboration between the National Marrow Donor Program (NMDP)/Be The Match and the Medical College of Wisconsin (MCW). The award is part of a program to increase racial and ethnic diversity in the next generation of medical professionals.

NMDP/Be The Match is proud to provide Dr. Agbedia mentorship and support research with ASH and the CIBMTR that will positively impact patients and expand representation in our field, said Stephen Spellman, Vice President, Research, NMDP/Be The Match. We believe that diversity, equity, and inclusion in our field are essential to innovation and eliminating health care disparities.

Dr. Agbedia is a fellow, Hematology/Oncology at UT MD Anderson Cancer Center and a graduate student at MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. Dr. Agbedia is interested in investigating an innovative cellular therapeutic option for treating CD94-expressing NK/T-cell lymphoproliferative disorders.

Along with our partner organizations, the CIBMTR is committed to supporting the career development of our next generation, particularly those with diverse backgrounds. In so doing, we ensure the future success of our field by fostering the minds and hearts of those who will discover novel approaches to improve patient outcomes, said CIBMTR Chief Scientific Director Jeffery Auletta, MD.

The award enrolls Dr. Agbedia in the American Society for Transplant and Cellular Therapy (ASTCT) Leadership and the ASTCT Clinical Research Training courses and includes membership on the ASTCT Committee on Diversity and Inclusion. Dr. Agbedia receives registration for the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR. Additionally, Dr. Agbedia will be invited to present research findings during the Promoting Minorities in Hematology event at the ASH Annual Meeting and Exposition.

The CIBMTR/American Society of Hematology, (ASH)/American Society of Transplantation and Cellular Therapy (ASTCT) award is part of the ASH Minority Hematology Fellow Award (MHFA) program, which supports early-career researchers from racial and ethnic groups that were historically underrepresented in medicine. This award is exclusively for fellows pursuing careers in hematopoietic stem cell transplantation and cellular therapy. It is one of six programs under ASHs Minority Recruitment Initiative, a series of programs committed to increasing racial and ethnic diversity in physicians training in hematology-related fields and in hematologists with academic and research appointments.

Background:

The National Marrow Donor Program (NMDP)/Be The Match is the leading global partner working to save lives through cellular therapy. With more than 35 years of experience managing the most diverse registry of potential unrelated blood stem cell donors and cord blood units worldwide, NMDP/Be The Match is a proven partner in providing cures to patients with life-threatening blood and marrow cancers and diseases. Its global network connects centers and patients to their best cell therapy option. It is a tireless advocate for the cell therapy community, working with hematologists/oncologists to remove barriers to consultation and treatment and supporting patients through no-cost programs to eliminate non-medical obstacles to cell therapy. NMDP/Be The Match is a global leader in research through the CIBMTR, investing in and managing research studies that improve patient outcomes and advance the future of care.

The CIBMTR (Center for International Blood and Marrow Transplant Research) is a research collaboration between the National Marrow Donor Program (NMDP)/Be The Match and the Medical College of Wisconsin (MCW). The CIBMTR collaborates with the global scientific community to advance hematopoietic cell transplantation (HCT) and cellular therapy worldwide to increase survival and enrich the quality of life for patients. The CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of transplant centers, and a unique and extensive clinical outcomes database. For more information on the CIBMTR, please visit http://www.cibmtr.org or follow the CIBMTR on Facebook, LinkedIn, or Twitter at @CIBMTR.

The American Society of Hematology (ASH) (www.hematology.org) is the worlds largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

The American Society for Transplantation and Cellular Therapy (ASTCT), with headquarters in Chicago, is a professional society over 3,000 00 healthcare professionals and scientists from more than 45 countries who are dedicated to improving the application and success of blood and marrow transplantation and related cellular therapies. ASTCT strives to be the leading organization promoting research, education and clinical practice to deliver the best, comprehensive patient care.

Excerpt from:
Dr. Owhofasa Agbedia Honored With The 2022 ASH-CIBMTR-ASTCT Career Development Award - Business Wire

Maintenance treatment with eprenetapopt, a novel drug, plus the chemotherapy Vidaza (azacitidine) following allogeneic hematopoietic stem cell transplantation was associated with improved survival outcomes in a group of patients with TP53-mutant, high-risk acute myeloid leukemia and myelodysplastic syndromes, according to new study findings.

Disease relapse is the primary reason why allogeneic hematopoietic stem cell transplants fail, according to the study authors, who noted that novel strategies for stem cell transplant to reduce the risk for disease relapse are severely needed.

Of note, an allogeneic hematopoietic stem cell transplant is a procedure where a patient with cancer receives healthy blood-forming stem cells from a donor to replace their own stem cells that have been damaged by other cancer treatments such as radiation or chemotherapy.

Currently, maintenance strategies (which are used to reduce the risk for disease recurrence) are not standard of care in allogeneic (hematopoietic stem cell transplant) for (acute myeloid leukemia and myelodysplastic syndromes), the study authors wrote.

In preclinical trials, eprenetapopt a small molecule drug that may reactivate mutant p53 proteins was active alongside Vidaza. Moreover, results from prior studies have shown the combination to be safe and effective in patients with other forms of blood cancers.

As a result, investigators aimed to see if maintenance therapy with eprenetapopt and Vidaza would induce similar results in this high-risk patient population.

They conducted a phase 2, multicenter trial to analyze if post-transplant eprenetapopt plus Vidaza improved relapse-free survival (which is the length of time following completion of primary treatment that a patient survives without signs or symptoms of that cancer). Based on prior results, the study investigators determined that a one-year relapse-free survival rate of 50% or greater would be considered successful.

A total of 84 patients were screened to determine if they were eligible for an allogeneic hematopoietic stem cell transplantation. Of the 55 patients who received a transplant, 33 patients (14 with acute myeloid leukemia and 19 with myelodysplastic syndromes) received maintenance treatment with eprenetapopt and Vidaza.

At a median follow-up of 14.5 months, maintenance therapy was associated with a median relapse-free survival of 12.5 months and an estimated one-year relapse-free survival rate of 59.9%. Additionally, the median overall survival (time from treatment to death of any cause) was 20.6 months at a median follow-up of 17 months. It was also estimated that the one-year overall survival rate was 78.8%.

Some of the most frequent severe or worse side effects to occur in the patient population included a decrease in white blood cell count (36%), anemia (27%) and hypertension (12%). There were four serious cases of fever and two serious cases each of febrile neutropenia (fever during a period of low white blood cell count) and difficult or labored breathing.

There were some occurrences of dose reduction (9%), interruption (6%) or delay (6%) because of treatment-related side effects.

Two patient deaths were reported during the study period one that was associated with a side effect not related to study treatment and one attributed to disease progression more than 30 days after study treatment completion.

TP53 mutation is associated with a poor prognosis in (acute myeloid leukemia) and (myelodysplastic syndromes), even in patients who undergo allogeneic (hematopoietic stem cell transplantation), the study authors wrote. Post-(hematopoietic stem cell transplantation) maintenance therapy with eprenetapopt plus (Vidaza) in this high-risk population of patients with TP53 mutant (acute myeloid leukemia) or (myelodysplastic syndromes) led to favorable survival outcomes. These data support future exploration of this maintenance strategy in a phase 3 study of eprenetapopt plus (Vidaza) versus placebo plus (Vidaza) in patients with TP53 mutant myeloid malignancies.

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Excerpt from:
Novel Drug-Chemotherapy Combo After Stem Cell Transplant Associated With 'Favorable Survival Outcomes' in Group of Rare Blood Cancers - Curetoday.com

Stephanie Si Lim

A therapy that helps modify a patients T cells (a type of immune cell) to make them more capable of fighting cancer was recently brought to Hawaii by Stephanie Si Lim, assistant professor at the University of Hawaii Cancer Center and pediatric hematologist oncologist at Kapiolani Medical Center for Women & Children. Chimeric Antigen Receptor T-cell therapy (CAR T-cell therapy) can result in the development of life-saving treatments for cancers that are difficult to treat.

Si Lim is leading the initiative at Kapiolani Medical Center for Women & Childrenpart of Hawaii Pacific Healthto build a broader cellular immunotherapy program. A key goal of the program is to introduce CAR T-cell therapy to the medical community in Hawaii in the form of clinical trials and U.S. FDA (Food and Drug Administration) approved products. This will ensure that patients have access to the best available treatments for cancer.

CAR T-cell therapy is now available to children and young adults with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia, and will soon be available to adult patients.

The first CAR T-cell clinical trial opened on May 14, 2022, at Kapiolani Medical Center for Women & Children, leveraging the infrastructure and expertise of the hospitals stem cell transplant and clinical research programs. Moving forward, all patients living in Hawaii, including the neighbor islands who qualify for this clinical trial, will be able to receive treatment on Oahu without having to travel to the continental U.S.

Si Lim said, We are so excited to be able to offer CAR T-cell therapy to our patients here in Hawaii. This is a momentous step for our medical community as we continue to strive to offer the best and most cutting-edge therapies to patients in need.

Currently, CAR T-cell therapy is proven to be particularly effective against B-cell malignancies and multiple myelomaboth common forms of cancer in adults and pediatric populations in Hawaii. Over the next few years, it is expected that new FDA-approved CAR T-cell treatments will also be available for other cancers in the state, including breast and prostate.

Go here to see the original:
Broadening access to cancer fighting therapy led by UH researcher | University of Hawaii System News - University of Hawaii

ROBERT KITCHIN/Stuff

Joan Perry, left, presents ACT deputy leader Brooke van Velden, right, with the petition calling for stem cell therapy to be available for people with multiple sclerosis in New Zealand.

A 10,000-strong petition to Parliament on Tuesday asking Health New Zealand to extend game-changing stem cell treatment to multiple sclerosis (MS) patients has been delivered to Parliament.

The petition was presented to ACT deputy leader Brooke van Velden who will present it to Parliament. The group of about 20 who presented the petition were joined by Green MP Golriz Ghahraman who also has MS.

Aucklander Joan Perry, whose daughter Anne Besley has MS, started the petition which calls for autologous haematopoietic stem cell transplantation (aHSCT) to be made available for selected patients in New Zealand.

Doctors extract blood stem cells and grow them in a laboratory, before the patient undergoes chemotherapy to suppress their immune system. The blood stem cells are then re-introduced back to the body to restart the immune response and stop the disease from getting worse.

READ MORE:* People with multiple sclerosis unable to access 'life-changing' treatment in NZ* Multiple sclerosis patient calls for 'life-changing' treatment to be funded in NZ* Multiple sclerosis sufferer says stem cell treatment in India has 'saved her life'

Anne Besleys MS has gone into remission since her stem cell treatment in 2019.

At present, it is only available in New Zealand for blood cancer patients.

Advocates for the treatment say it is already proven and readily available in Australia and the UK for patients exhibiting early and aggressive symptoms.

Besley, a former operating theatre nurse at Aucklands Middlemore Hospital, had to go to India for the treatment in late 2019 at a cost of $42,000. Since then, her MS has gone into remission, allowing her to return to nursing part-time as a Covid-19 vaccinator.

It comes with huge financial and mental challenges, she said. Being isolated in a foreign country for a month is an emotional and physical struggle, especially when you are so weak while undergoing treatment and having a severely compromised immune system.

ROBERT KITCHIN/Stuff

Green MP Golriz Ghahraman (far left), who has MS, says she would consider the stem cell treatment if it is available in New Zealand. Right: Joan Perry, who started the petition calling for stem cell therapy to be made available for MS patients.

Ghahraman said she would consider stem cell treatment if it was available in New Zealand and hoped the petition would have an impact for public healthcare to provide the most effective options to everyone regardless of their means.

People are ruling it out because they know they cant afford it, she said. In New Zealand, its very few people who would ever be in a position to go.

Van Velden said New Zealand needed better oversight and transparency about the types of medicines and treatment that New Zealanders have access to.

I would like to see more forward planning in New Zealand about the newer medicines, she said. We are falling behind the rest of the world.

ROBERT KITCHIN/Stuff

Brooke van Velden, right, wants to see better forward planning for medicine and treatment options in New Zealand. Left: Petitioner Joan Perry.

Bronwyn Hutchison is a Wellington mother of two who was diagnosed with MS in 2011. She is already on drug-based treatment in New Zealand, meaning trips to hospital for infusions every six weeks and the side effects taking a physical toll.

Hutchison came across stem cell treatment in her research in 2019 after a painful relapse.

She attended a private clinic in Mexico to get the four-week treatment, but had to raise more than $100,000. There have been had been no relapses in the three years since.

I didnt have that money sitting around, she said. That was a year of my family and friends using all their spare time, and I was really lucky with the community support.

My daughter, who's now 9, is still recovering from the effects of me leaving for a month and thinking I might die. I don't think the trauma would have been the same if I had been able to have the treatment here.

Supplied

Bronwyn Hutchison had to travel to Mexico to receive Autologous Haematopoietic Stem Cell Transplantation for her MS diagnosis as it is not available in New Zealand.

Multiple Sclerosis Society of New Zealand, which has been asking the Ministry of Health for five years to approve and fund stem cell treatment for MS, backed the petition.

President Neil Woodhams said patients were fed up waiting for it to be made available here, while more than 100 had gone overseas to countries like Singapore, Mexico, India and Russia for self-funded treatment.

People are still going overseas for treatment and in a Covid environment, it is risky, he said. It is a one-off treatment and if it is successful, they don't have to worry about taking a drug every day or week or going to the hospital every six months.

Read this article:
Petition calling for 'life-changing' MS treatment funding handed to Parliament - Stuff

Lifestyle diseases are gradually moving up the ranks causing deaths globally. Liver diseases appear to be one such condition, with a significantly increased number of patients being diagnosed each year. According to the WHO data published in 2017, liver disease was responsible for around 2.95% of the total deaths in India, accounting for one-fifth of all cirrhosis-associated deaths globally. Earlier, infections such as hepatitis B and C were the main causes; however, alcohol consumption and obesity are now becoming bigger contributors to liver disease.We know that the liver is responsible for detoxifying alcohol and drugs, but also performs multiple other functions, including glucose supply to the brain, food digestion, producing blood during foetal development, storing nutrients, etc. We also know that the liver can regenerate, but that does not mean a fully damaged liver can grow back on its own. Therefore, it is important to pay attention to signs of liver disease and initiate treatments promptly.Liver cirrhosisCirrhosis is a condition where scars form in the liver causing the normal liver tissue to harden, thereby preventing the effective functioning of the organ. Cirrhosis and liver cancer are the prime causes of death due to liver disease globally. Regenerative medicine researcher Dr Pradeep Mahajan shares that alcohol consumption, viral hepatitis, autoimmune diseases, non-alcoholic fatty liver disease, and several inherited metabolic disorders can cause cirrhosis.The disease process begins as inflammation (swelling) in the liver tissue followed by scar formation and ultimately liver failure. Considering that there is no cure for cirrhosis per se, symptom and lifestyle management remain the mainstay of conventional treatment. Liver transplantation is the only curative option for severe cases; however, the issue of organ shortage is a chief and ever-growing concern.How can one get treated?Dr Mahajan says: Since we know that the liver can regenerate itself, the way ahead is to diagnose the liver disease as early as possible and find ways to enhance its regenerative potential. This is where cell and growth factor-based therapy can be beneficial.Stem cells in our body are capable of differentiating into liver (and various other) cells. In addition, they are also capable of regulating the immune system, reducing inflammation, enhancing blood supply, and stimulating other cells to perform their functions more efficiently. Similarly, growth factors can be isolated from blood/platelets, which serve as nutrition for cells of the body. These can help in cirrhosis by stabilising the internal environment of the liver making it more conducive to healing and regeneration.We are simply trying to find ways to capitalise on the healing potential of the liver before issues like scarring happen. Of course, lifestyle modification will be required to enhance the outcomes, but the end goal is to prevent the need for (or at least delay) liver transplantation, which can significantly affect a patients quality of life, adds Dr Mahajan.

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How effective is stem cell therapy for liver cirrhosis? - Times of India

Tecartus (Brexucabtagene Autoleucel) First and Only CAR T in Europe to Receive Positive CHMP Opinion to Treat Adults 26+ with r/r ALL

If Approved, it will Address a Significant Unmet Need for a Patient Population with Limited Treatment Options

SANTA MONICA, Calif.--(BUSINESS WIRE)--Kite, a Gilead Company (Nasdaq: GILD), today announces that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Tecartus (brexucabtagene autoleucel) for the treatment of adult patients 26 years of age and above with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (ALL). If approved, Tecartus will be the first and only Chimeric Antigen Receptor (CAR) T-cell therapy for this population of patients who have limited treatment options. Half of adults with ALL will relapse, and median overall survival (OS) for this group is only approximately eight months with current standard-of-care treatments.

Kites goal is clear: to bring the hope of survival to more patients with cancer around the world through cell therapy, said Christi Shaw, CEO, Kite. Todays CHMP positive opinion in adult ALL brings us a step closer to delivering on the promise that cell therapies have to transform the way cancer is treated.

Following this positive opinion, the European Commission will now review the CHMP opinion; the final decision on the Marketing Authorization is expected in the coming months.

Adults with relapsed or refractory ALL often undergo multiple treatments including chemotherapy, targeted therapy and stem cell transplant, creating a significant burden on a patients quality of life, said Max S. Topp, MD, professor and head of Hematology, University Hospital of Wuerzburg, Germany. If approved, patients in Europe will have a meaningful advancement in treatment. Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care.

Results from the ZUMA-3 international multicenter, single-arm, open-label, registrational Phase 1/2 study of adult patients (18 years old) with relapsed or refractory ALL, demonstrated that 71% of the evaluable patients (n=55) achieved complete remission (CR) or CR with incomplete hematological recovery (CRi) with a median follow-up of 26.8 months. In an extended data set of all patients dosed with the pivotal dose (n=78) the median overall survival for all patients was more than two years (25.4 months) and almost four years (47 months) for responders (patients who achieved CR or CRi). Among efficacy-evaluable patients, median duration of remission (DOR) was 18.6 months. Among the patients treated with Tecartus at the target dose (n=100), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 25% and 32% of patients, respectively, and were generally well-managed.

About ZUMA-3

ZUMA-3 is an ongoing international multicenter (US, Canada, EU), single arm, open label, registrational Phase 1/2 study of Tecartus in adult patients (18 years old) with ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation. The primary endpoint is the rate of overall complete remission or complete remission with incomplete hematological recovery by central assessment. Duration of remission and relapse-free survival, overall survival, minimal residual disease (MRD) negativity rate, and allo-SCT rate were assessed as secondary endpoints.

About Acute Lymphoblastic Leukemia

ALL is an aggressive type of blood cancer that develops when abnormal white blood cells accumulate in the bone marrow until there isnt any room left for blood cells to form. In some cases, these abnormal cells invade healthy organs and can also involve the lymph nodes, spleen, liver, central nervous system and other organs. The most common form is B cell precursor ALL. Globally, approximately 64,000 people are diagnosed with ALL each year, including around 3,300 people in Europe.

About Tecartus

Please see full FDA Prescribing Information, including BOXED WARNING and Medication Guide.

Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred following treatment with Tecartus. In ZUMA-2, CRS occurred in 91% (75/82) of patients receiving Tecartus, including Grade 3 CRS in 18% of patients. Among the patients who died after receiving Tecartus, one had a fatal CRS event. The median time to onset of CRS was three days (range: 1 to 13 days) and the median duration of CRS was ten days (range: 1 to 50 days). Among patients with CRS, the key manifestations (>10%) were similar in MCL and ALL and included fever (93%), hypotension (62%), tachycardia (59%), chills (32%), hypoxia (31%), headache (21%), fatigue (20%), and nausea (13%). Serious events associated with CRS included hypotension, fever, hypoxia, tachycardia, and dyspnea.

Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility, and for four weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

Neurologic Events, including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in 81% (66/82) of patients with MCL, including Grade 3 in 37% of patients. The median time to onset for neurologic events was six days (range: 1 to 32 days) with a median duration of 21 days (range: 2 to 454 days) in patients with MCL. Neurologic events occurred in 87% (68/78) of patients with ALL, including Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.

The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus.

Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly.

REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that:

Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus.

Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. Infections (all grades) occurred in 56% (46/82) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients with ALL and MCL. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Tecartus infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 6% of patients with MCL and 35% of patients with ALL after Tecartus infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of febrile neutropenia (11 (14%)) plus the concurrent events of fever and neutropenia (16 (21%)). In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Tecartus infusion. In patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% (45/82) of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). In patients with ALL who were responders to Tecartus treatment, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following Tecartus infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after Tecartus infusion.

Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of patients with MCL and 9% (7/78) of patients with ALL. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during Tecartus treatment, and until immune recovery following treatment with Tecartus.

Secondary Malignancies may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period.

Adverse Reactions: The most common non-laboratory adverse reactions ( 20%) were fever, cytokine release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The most common serious adverse reactions ( 2%) were cytokine release syndrome, febrile neutropenia, hypotension, encephalopathy, fever, infection with pathogen unspecified, hypoxia, tachycardia, bacterial infections, respiratory failure, seizure, diarrhea, dyspnea, fungal infections, viral infections, coagulopathy, delirium, fatigue, hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema, and paraparesis.

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kites singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. For more information on Kite, please visit http://www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials, including those involving Tecartus; the risk that physicians may not see the benefits of prescribing Tecartus for the treatment of blood cancers; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gileads Quarterly Report on Form 10-Q for the quarter ended March 31, 2022 as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

U.S. Prescribing Information for Tecartus including BOXED WARNING, is available at http://www.kitepharma.com and http://www.gilead.com .

Kite, the Kite logo, Tecartus and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies .

View source version on businesswire.com: https://www.businesswire.com/news/home/20220722005258/en/

Jacquie Ross, Investorsinvestor_relations@gilead.com

Anna Padula, Mediaapadula@kitepharma.com

Source: Gilead Sciences, Inc.

More:
Kite's CAR T-cell Therapy Tecartus Receives Positive CHMP Opinion in Relapsed or Refractory Acute Lymphoblastic Leukemia (r/r ALL) - Gilead Sciences

SINGAPORE - A Singaporean doctorwho is one of the top cell therapy experts in the worldhas been appointed to a World Health Organisation (WHO) expert panel.

Dr Mickey Koh is so sought-after in his field that for the past 15 years, he has been holding two jobs in two different countries.

The 56-year-old shuttles between England and Singapore, spending six weeks at a time in London, where he oversees the haematology department and looks after bone marrow transplant patients at St George's University Hospital, before returning to Singapore for a week and a half to head the cell therapy programme at the Health Sciences Authority.

Cell therapy is a growing field of medicine that uses living cells as treatment for a variety of diseases and conditions. This is an increasingly important therapeutic area and both his employers have agreed to his unusual schedule.

Over in London, Dr Koh is head of the Haematology Department at St George's Hospital and Medical School. In Singapore, he is the programme and medical director of the cell and gene therapy facility at the Health Sciences Authority.

In May, Dr Koh was selected to be on the WHO Expert Advisory Panel on Biological Standardisation.

Individuals on the panel have to be invited by WHO to apply, and are well recognised in their respective scientific fields. Eminent names on the panel include the current president of the Paul-Ehrlich-Institut in Germany, which is the country's federal agency, medical regulatory body and research institution for vaccines and biomedicine.

The WHO panel, which is made up of about 25 members, provides detailed recommendations and guidelines for the manufacturing, licensing and standardisation of biological products, which include blood, monoclonal antibodies, vaccines and, increasingly, cell-based therapeutics.

The recommendations and advice are passed on to the executive board of the World Health Assembly, which is the decision-making body of WHO.

Dr Koh's role had to be endorsed by the British government and was a direct appointment by the director-general of WHO.

His appointment as a panel expert will last for a term of four years.

Speaking to The Straits Times, Dr Koh shared his thoughts about the importance of regulation: "We are well aware that there is a very lucrative worldwide market peddling unproven stem cell treatments, where side effects are often unknown, and such unregulated practice can result in serious harm.

"This is already happening. People are claiming that you can use stem cells to treat things like ageing, and even very serious conditions like strokes, without any evidence."

With many medications now taking the form of biologics - a drug product derived from biological sources such as cells - the next wave of treatment would be the utilisation of these cells for the treatment of a wide range of diseases, Dr Koh said.

Read the original here:
S'porean doctor, a sought-after top expert in cell therapy, appointed to WHO expert panel - The Straits Times

Many clinicians believe the most significant advance in LBCL treatment in this time is the development of chimeric antigen receptor T-cell therapy.

Over the past 10 years, treatment options for patients with large B-cell lymphomas (LBCLs) have expanded with the approval of several new classes of treatment.

Many clinicians believe the most significant advance in LBCL treatment in this time is the development of chimeric antigen receptor (CAR) T-cell therapy.

I definitely think that this is the most notable agent in the last 10 years, said Sarah Rutherford, MD, an assistant professor of medicine and the John P. Leonard, MD/Gwirtzman Family Research Scholar in Lymphoma at Weill Cornell Medical College, Cornell University, in an interview with Targeted Therapies in Oncology.

Brian T. Hill, MD, PhD, director of the Lymphoid Malignancies Program and a staff physician at Cleveland Clinic Taussig Cancer Institute, agreed. Because there are now patients 5 years out without any signs of relapse with a single treatment of cell therapy 5 years ago, I think its pretty clear that is curative therapy in a proportion of patients who otherwise wouldnt be alive. The clinical impact on patients who received it really cant be understated.

Many subtypes of LBCL have been recognized.1,2 Their clinical and pathologic heterogeneity contributes to variations in prognosis and response to treatment.3,4

In 2012, standard treatment was chemoimmunotherapy with the anti-CD20 monoclonal antibody rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Response rates in this rituximab era were 80% to 90% in low-risk diffuse LBCL (DLBCL), but 5-year overall survival (OS) rates were only 30% to 50%, indicating a need for additional personalized therapies to improve outcomes, especially following standard R-CHOP therapy.3

CAR-T cells are produced from autologous patient T cells transduced with CARs engineered to bind to a specific tumor antigen via an extracellular domain, CD19 for B-cell malignancies, and containing costimulatory molecules.5 These agents have been welcomed into the treatment paradigm due to high response and survival rates.

Axicabtagene ciloleucel (Yescarta) received FDA approval in 2017 for the treatment of relapsed/ refractory (R/R) DLBCL, primary mediastinal B-cell lymphoma (PMBCL), high-grade BCL, and transformed follicular lymphoma (FL). In 2019, the agency approved the drug for patients with LBCL that had progressed on 2 prior therapies; in 2021, for R/R FL, and in April 2022, for LBCL refractory to or relapsing within 12 months of first-line chemoimmunotherapy (TIMELINE). 5-7

Tisagenlecleucel (Kymriah) was approved in 2018 for adult R/R LBCL, including DLBCL, highgrade BCL, and DLBCL arising from FL.5,8

In 2021, the FDA approved lisocabtagene maraleucel (Breyanzi) for patients with R/R LBCL, including DLBCL, high-grade BCL, PMBCL, and FL grade 3B after at least 2 lines of systemic therapy.5,9 Then in June 2022, the agency approved the CAR T-cell therapy for those with LBCL refractory to or relapsing within 12 months of first-line chemoimmunotherapy.10

CAR T-cell therapy is associated with potentially life-threatening toxicities, including cytokinerelease syndrome and neurologic toxicities, although advances in management have improved outcomes. Loss of the target antigen, CD19, renders treatment ineffective.1,11,12

Although CAR-T therapy results in effective and durable clinical responses for about 40% of patients, not all patients are even candidates due to age, comorbidities, or lack of chemotherapysensitive disease. The length of time required to manufacture this individualized therapy may be too long for those with rapidly progressive disease to wait.11,12 Further, few facilities are able to administer CAR T-cell therapy, as they must be accredited by the Foundation for the Accreditation of Cellular Therapy, making access also an issue.

For those who cant receive CAR T-cell therapy, there are 4 other FDA-approved targeted therapies: polatuzumab vedotin [Polivy], selinexor [Xpovio], tafasitamab [Monjuvi] administered with lenalidomide [Revlimid], and loncastuximab tesirine [Lonca, Zynlonta]. We can tailor our targeted approach to each individual patient in a way much better than we could before because we have many different options, Rutherford said.

R-CHOP as standard therapy has endured for 2 decades despite attempts to improve upon it with added chemotherapy or novel agents.13 More than half of patients who receive R-CHOP can be cured; the survival of those who are event free for 2 years is equivalent to that of an age- and sex-matched population; 10% to 20% have primary refractory disease that is nonresponsive to R-CHOP; and 30% to 40% experience relapse after achieving a complete response (CR) to treatment.14

In 2017, the FDA approved a new formulation of rituximab (Rituxan Hycela), allowing rituximab to be administered via subcutaneous injection in a few minutes rather than an hours-long intravenous infusion, to patients with DLBCL, among other indications.15

Tafasitamab, a cytolytic, humanized, monoclonal antibody directed against CD19, was granted accelerated approval by the agency in 2020 in combination with lenalidomide followed by tafasitamab monotherapy in adults with R/R DLBCL who were not eligible for autologous stem cell transplant. In the open-label single-arm phase 2 L-MIND trial (NCT02399085), the best overall response rate (ORR) was 57.5% (95% CI, 45.9%-68.5%) after at least 35 months of follow-up, with a 40% CR rate. Responses were durable, with a median duration of 43.9 months (95% CI, 26.1-not reached).16,17

There are 2 recognized cell of originbased subtypes of DLBCL: germinal center B cell (GCB) and activated B cell (ABC). Classification of these distinct subtypes was added to the 2016 revision of the World Health Organizations classification of lymphoid neoplasms.2

Patients treated with R-CHOP who have the GCB subtype, which is more common, have better outcomes than those with the ABC subtype.18,19 The current frontline standard of care is the same for both subtypes. Immunohistochemistry (IHC) algorithms can be used to distinguish GCB from nonGCB, although the non-GCB subtype is more heterogeneous than the ABC subtype by gene expression profiling.1

Immunophenotyping by IHC is used for risk stratification as well as diagnosis, and includes CD20, CD3, CD5, CD10, CD45, BCL2, BCL6, Ki-67, IRF4/MUM1, and MYC. The presence of MYC plus either BCL2 or BCL6 by IHC should be followed by fluorescence in situ hybridization or karyotyping to detect rearrangements of these genes.1

Lymphomas with rearrangements of MYC and BCL2 and/or BCL6 (double-hit or triplehit, usually GCB subtype) have become classified as high-grade lymphomas over the past 6 years, and account for about 4% to 8% of all LBCL cases.2,19 Intensified induction treatment is preferred for these patients as outcomes with R-CHOP treatment are poor. When MYC and BCL2 are overexpressed (double-expressor, usually ABC subtype) rather than rearranged, prognosis may also be poor, and improved with intensified induction. Primary DLBCL of the central nervous system (typically ABC subtype) is rare, and is also associated with poor prognosis.18,19

Although understanding molecular and genetic subtypes can enhance treatment allotment in clinical studies, a unified model appropriate for clinical practice has not yet been defined.18

Antibody-drug conjugates selectively deliver cytotoxic agents to malignant cells by linking a monoclonal antibody that targets an antigen on those cells with a cytotoxic payload.4

Polatuzumab vedotin combines an antiCD79b monoclonal antibody with a potent microtubule inhibitor. It was granted accelerated approval by the FDA in 2019 in combination with bendamustine and rituximab (BR) for the treatment of adults with R/R DLBCL after at least 2 prior therapies. The CR rate for polatuzumab plus BR was 40% vs 18% with BR alone, with best ORR of 63% and 25%, respectively.20

Polatuzumab showed activity in a phase 1b/2 trial (NCT01992653) as first-line therapy for DLBCL with rituximab plus cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP), eliminating vincristine from CHOP to avoid the overlapping neurologic toxicity with polatuzumab. Responses were seen in 89% of patients and CRs in 77%.21

The double-blind phase 3 POLARIX trial (NCT03274492) compared pola-R-CHP with R-CHOP in patients with previously untreated, intermediate, or high-risk DLBCL. At a median follow-up of 28.2 months, 76.7% of patients in the pola-R-CHP group survived without progression at 2 years vs 70.2% of the R-CHOP group (HR for progression, relapse, or death, 0.73; 95% CI, 0.57-0.95; P = .02). There was no significant difference in OS rates at 2 years (88.7% with pola-RCHP vs 88.6% with R-CHOP; HR, 0.94; 95% CI, 0.65-1.37; P = .75). The safety profile was also comparable between the groups.22

Lonca combines a humanized anti-CD19 monoclonal antibody with an alkylating cytotoxin causing interstrand DNA crosslinks.23

Lonca monotherapy received accelerated approval in 2021 for patients with R/R LBCL, including DLBCL and high-grade BCL, after at least 2 lines of systemic therapy based on the results of the open-label, single-arm LOTIS-2 trial in DLBCL (NCT03589469). Participants in the phase 2 study included those with highrisk, poor prognosis, and double- and triple-hit lymphoma after at least 2 prior regimens. The ORR was 48.3% (95% CI, 39.9%-56.7%), including a CR rate of 24.1%. The median duration of response was 10.3 months.23,24

Responses in patients who had received prior CD19-directed CAR T-cell therapy (n = 13) were similar to those of study patients overall (n = 145), although enrollment required persistent CD19 expression. Treatment with Lonca also did not interfere with response to subsequent CAR T-cell therapy (n = 15; ORR, 47%), suggesting Lonca could be used either as salvage therapy after CAR T-cell therapy or as an alternative or bridging therapy for those with rapidly progressing disease without compromising subsequent CAR T-cell therapy.23

Recently, the addition of lenalidomide to brentuximab vedotin (Adcetris), an antiCD30 monoclonal antibody with a tubulin disrupting agent, was explored in a phase 1 dose-expansion trial (NCT02086604) in patients with R/R DLBCL. The combination was well tolerated, although most patients had neutropenia requiring granulocyte colony-stimulating factor support. The ORR was 57% (95% CI, 39.6%-72.5%) and the CR rate was 35%, with a median duration of response of 13.1 months.25

Selinexor is an oral, selective small molecule inhibitor of XPO1-mediated nuclear export. It received accelerated approval in 2020 for adults with R/R DLBCL after 2 to 5 prior lines of therapy, including progression after or ineligibility to undergo transplant. In the single-arm, open-label phase 2 SADAL trial (NCT02227251) in heavily pretreated patients, the ORR was 28% (95% CI, 20.7%- 37.0%) and the CR rate was 12%. The disease control rate was 37% (95% CI, 28.6%-46.0%) and the median duration of response was 9.3 months (95% CI, 4.8-23.0). The most common grade 3 or higher AEs were cytopenias.1,26,27

The safety and efficacy of venetoclax (Venclexta), a selective BCL2 inhibitor approved for other hematologic malignancies, was assessed in the phase 2 CAVALLI trial (NCT02055820) in combination with R-CHOP in patients with treatment-nave DLBCL overexpressing BCL2 protein by IHC. At a median follow-up of 32.3 months, the ORR was 83% and the CR rate was 69%. Treatment was associated with increased, manageable myelosuppression. A cross-trial comparison with the GOYA trial (NCT01287741) of standard R-CHOP did not show a progression-free survival advantage.28

Involved-site radiation therapy (ISRT) can follow R-CHOP first-line therapy for bulky stage I and II DLBCL without extensive mesenteric disease. This form of therapy is recommended for patients who are not candidates for chemoimmunotherapy.1

Those with DLBCL that relapses after more than 12 months can be considered for transplant. After second-line therapy, transplant-eligible patients who experience CR or partial response can receive high-dose therapy with autologous stem cell rescue, or in some cases allogeneic hematopoietic cell transplant.1

Bispecific antibodies simultaneously target tumor and immune cell antigens. Several are in development for B-cell lymphomas, including blinatumomab (Blincyto), which binds CD19 and CD3, and mosunetuzumab and glofitamab, which bind both CD20 and CD3.18,29-31 Hill said bispecific antibodies are highly active in R/R lymphomas and appear to be free of many of the toxicities seen with CAR T cells. He speculated that for patients unable to receive CAR T- cell treatment because they are unable to travel to a referral center, bispecific antibodies are likely to be widely available in the community setting, eventually.

Hill said, Theres a lot of excitement about the possibility of delivering therapies that dont require individual patient manufacturing. These could include off-the-shelf cellular therapies.

Approaches may include adoptive transfer of cytotoxic natural killer (NK) cells, which, unlike T cells, are not associated with cytokine release syndrome or graft-vs-host disease. This will rely on pre-expanded, banked cells from different sources to allow transfer with minimal human leukocyte antigen matching.32

In addition to NK cells, other immune effector cells such as invariant NK T cells, - T cells, and macrophages may be amenable to engineering into alternative CAR constructs to treat R/R B-cell malignancies.12

Other biomarkers that may provide treatment targets are being investigated. TP53 mutations are frequently found in patients with R/R DLBCL and are considered a negative prognostic indicator.33 These mutations have also been associated with acquired resistance to rituximab and R-CHOP failure.18 Currently, use of locoregional therapy shows the best survival outcomes for patients with these mutations.33

Magrolimab, which targets CD47, a molecule that when overexpressed in tumor cells allows them to evade phagocytosis, has shown activity in an early trial.18,19

Mutations in the histone-methyl transferase EZH2 have been reported in about 25% of GCB lymphomas. The oral EZH2 inhibitor tazemetostat (Tazverik), which is already approved for EZH2-mutation positive R/R FL after at least 2 prior therapies or if there are no other treatment options, has shown initial encouraging efficacy in combination with R-CHOP in untreated DLBCL, and should be further investigated.34,35

Pembrolizumab, a humanized antiPD-1 monoclonal antibody, is approved for treatment of patients with R/R PMBL after at least 2 prior lines of therapy.1 Otherwise, immunotherapy with immune checkpoint inhibitors (ICIs) has not been effective in DLBCL, although a retrospective analysis suggested ICIs could sensitize lymphomas to subsequent chemotherapy.4 Combinations of ICIs with R-CHOP or other agents are under investigation.18

There are still people with really aggressive diseases that just dont respond to anything you give them. Trying to figure out who they are and why thats happening, and trying to figure out the better targeted approach earlier on, is what I view as the biggest unmet need, Rutherford said.

Its been a fulfilling time to be a researcher and to care for these patients because we used to have not much to offer for them, and even though we do prefer clinical trials for people when we can, there are reasons why people cant get on trials, whether its comorbidities or lack of availability of trials, etc. Its been very fulfilling now to have a lot of options for people to talk about, rather than just giving [these patients] different types of chemotherapy that is unlikely to work, Rutherford said.

Hill agreed. It has been a very remarkable time, he said. I have been at this 11 years, and the treatment options that have been available in 2022 compared [with] 2012 are remarkably improved and likely to be even better in the future.

REFERENCES:

1. NCCN Clinical Practice Guidelines in Oncology. B-cell lymphomas. Version 4.2022. June 9, 2022. AccessedJune 10, 2022. https://bit.ly/3I8Urdh

2. Swerdlow SH, Campo E, PileriSA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390. doi:10.1182/blood-2016-01-643569

3. Cultrera JL, Dalia SM. Diffuse large B-cell lymphoma: current strategies and future directions. Cancer Control. 2012;19(3):204-213. doi:10.1177/107327481201900305

4. Susanibar-Adaniya S, Barta SK. 2021 update on diffuse large B cell lymphoma: a review of current data and potential applications on risk stratification and management. Am J Hematol.2021;96(5):617-629. doi:10.1002/ajh.26151.

5. Gill S, Brudno JN. CAR T-cell therapy in hematologic malignancies: clinical role, toxicity, and unanswered questions. Am Soc Clin Oncol Educ Book. 2021;41:1-20. doi:10.1200/EDBK_320085

6. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. FDA. April 1, 2022. Accessed June 10, 2022. https://bit.ly/3AcxUdw

7. Milestones in cancer research and discovery. NIH. Accessed June 10, 2022. https://bit.ly/3OOcmblFDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma. FDA. May 1, 2018. Accessed June 10, 2022. https://bit.ly/2kX8e0h

8. FDA approves lisocabtagene maraleucel for relapsed or refractory large B-cell lymphoma. FDA. February 5, 2021. Accessed June 10, 2022. https://bit.ly/3QY8Ixh

9. FDA approves lisocabtagene maraleucel for second-line treatment of large B-cell lymphoma. FDA. June 24, 2022. Accessed June 27, 2022. https://bit.ly/3yvnW60

10. Abramson JS. Anti-CD19 CAR T-cell therapy for B-cell non-Hodgkin lymphoma. Transfus Med Rev. 2020;34(1):29-33. doi:10.1016/j.tmrv.2019.08.003Basar R, Daher M, Rezvani K. Next-generation cell therapies: the emerging role of CAR-NK cells. Blood Adv. 2020;4(22):5868-5876. doi:10.1182/bloodadvances.2020002547

11. Leonard JP. De-cell-eration in therapy for diffuse large B-cell lymphoma. J Clin Oncol. 2019;37(15):1267-1269. doi:10.1200/JCO.19.00445

12. Goy A. Succeeding in breaking the R-CHOP ceiling in DLBCL: learningfrom negative trials. J Clin Oncol. 2017;35(31):3519-3522. doi:10.1200/JCO.2017.74.7360

13. New rituximab formulation approved for some lymphomas, leukemia. NIH. July 14, 2017. Accessed June 10, 2022. https://bit.ly/3ucnQ0q

14. DuellJ, Maddocks KJ, Gonzalez-Barca E, et al. Long-term outcomes from the phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021;106(9):2417-2426. doi:10.3324/haematol.2020.275958

15. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. July 31, 2020. Accessed June 10, 2022. https://bit.ly/3OS0xAO

16. Danilov AV, Magagnoli M, MatasarMJ. Translating the biology of diffuse large B-cell lymphoma into treatment. Oncologist.2022;27(1):57-66. doi:10.1093/oncolo/oyab004

17. Sehn LH, Salles G. Diffuse large B-cell lymphoma. New Engl J Med. 2021;384(9):842-858. doi:10.1056/NEJMra2027612

18. FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. FDA. June 10, 2019. Accessed June 10, 2022. https://bit.ly/2XEazLP

19. Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019;20(7):998-1010. doi:10.1016/S1470-2045(19)30091-9

20. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. New Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304

21. Caimi PF, Ai E, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800.doi:10.1016/S1470-2045(21)00139-X

22. FDA grants accelerated approval to loncastuximab tesirine-lpyl for large B-cell lymphoma. FDA. April 23, 2021. Accessed June 10, 2022. https://bit.ly/3QWReBy

23. Ward JP, Berrien-Elliott MM, Gomez F, et al. Phase 1/dose expansion trial of brentuximab vedotin and lenalidomide in relapsed or refractory diffuse large B-cell lymphoma. Blood. 2022;139(13):1999-2010.doi:10.1182/blood.2021011894

24. FDA approved selinexor for relapsed/refractory diffuse large B-cell lymphoma. FDA. June 22, 2020. Accessed June 10, 2022. https://bit.ly/3ONuxOk

25. Kalakonda N, MaerevoetM, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):511-522. doi:10.1016/S2352-3026(20)30120-4

26. Morschhauser F, Feugier P, Flinn IW, et al. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma. Blood. 2021;137(5):600-609.doi:10.1182/blood.2020006578

27. Budde LE, Assouline S, SehnLH, et al. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: phase I dose-escalation study. J Clin Oncol. 2021;40(5):481-491.doi:10.1200/JCO.21.00931

28. Dufner V, Sayehli CM, Chatterjee M, et al. Long-term outcome of patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with blinatumomab. Blood Adv. 2019;3(16):2491-2498.doi:10.1182/bloodadvances.2019000025

29. Hutchings M, Morschhauser F, IacoboniG, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial.J Clin Oncol. 2021;39(18):1959-1970. doi:10.1200/JCO.20.03175

30. Lamb MG, Rangarajan HG, Tullius BP, et al. Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future. Stem Cell Res Ther. 2021;12(1):211. doi:10.1186/s13287-021-02277-x

31. Qin Y, Jiang S, Liu P, et al. Characteristics and management of TP53-mutated diffuse large B-cell lymphoma patients. Cancer Manag Res. 2020;12:11515-11522. doi:10.2147/CMAR.S269624

32. FDA granted accelerated approval to tazemetostat for follicular lymphoma. FDA. June 18, 2020. Accessed June 10, 2022. https://bit.ly/3y76Rh1

33. Sarkozy C, Morschhauser F, Dubois S, et al. A LYSA phase 1b study of tazemetostat (EPZ-6438) plus R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with poor prognosis features. Clin CancerRes.2020;26(13):3145-3153.doi:10.1158/1078-0432.CCR-19-3741

Read more:
Top 10 Advances in Large B-Cell Lymphomas in the Past 10 Years - Targeted Oncology

Key Companies Covered in the Stem Cell Therapy Market Research are Vericel Corporation., Stem Cells, Inc., Mesoblast, Ltd., Gamida Cell, Osiris Therapeutics, Inc., Chiesi Farmaceutici S.p.A, ReNeuron Group, plc and other key market players.

Stem Cell Therapy Market is worth USD 11.99 billion in 2016 and is expected to reach USD 60.94 billion by 2022, growing at a CAGR of 31.1% from 2016 to 2022.

The global stem cell therapy market report offers in-depth analysis of the market size (revenue), market share, major market segments, different geographic regions, forecast for the next five years, key market players, and premium industry trends. It also focuses on the key drivers, restraints, opportunities and challenges in the stem cell therapy market.

KEY BENEFITS OF THE REPORT:Deeper understanding of the strategies adopted by the key players in this market to stay competitiveGranular analysis about the growth map of the market during the next five yearsComprehensive analysis of the key market players and their market share

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KEY PREMIUM INDUSTRY INSIGHTS:The increasing government initiatives and funding from various organizations, the increased spending on research and development, rapid technological advancement in genomics, and the rising awareness about the stem cell therapy are some of the factors fuelling the growth of the stem cell therapy market.Other factors, such as the robust product pipelines and increasing approval of the new clinical trials are fuelling the growth of the stem cell therapy market further.However, improper infrastructure, insufficient storage systems, and ethical problems are the major restraints for the stem cell therapy market.

MARKET SEGMENTATION:This report analyzes the stem cell therapy market by the following segments:

Stem Cell Therapy Market, by TreatmentsAllogeneic Stem Cell TherapyAutologous Stem Cell Therapy

Stem Cell Therapy Market, by ApplicationsOncologyCentral Nervous System DiseasesEye DiseasesMusculoskeletal DiseasesWound & InjuriesMetabolic DisordersCardiovascular DisordersImmune System Disorders

Stem Cell Therapy Market, by End-usersHospitalsAmbulatory Surgical Centers

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Stem Cell Therapy Market Emerging Trends to Make Driving Growth on Key Players Status - Taiwan News

Introduction

Stem cells are highly specialized cell types with an impressive ability to self-renew, able to transform into one or even more specific cell types that play a significant role in the regulation and tissue healing process.17 To self-renew, a stem divides into two identical daughter stem cells and a progenitor cell and the embryonic and adult cells contain stem cells.1,2,8

Curing patients with serious medical conditions has been the focus of all disciplines of medical research for many years. Stem cell treatment has evolved into a highly exciting and progressed field of scientific research. Major advances have recently been introduced in fundamental and translational stem-cell-based treatment studies. As stem cell research progressed, many therapeutic options were investigated. The development of therapeutic procedures has sparked a great deal of interest.1,9 Humanity has known for many years that it is possible to regenerate lost tissue. Recently, the regenerative medicine research has taken hold, defying the tremendous scientific advances in the molecular biology sciences only. Technological advances provide limitless opportunities for transformational and potentially restorative therapies for many of humanitys most illnesses. A variety of human organs have successfully yielded stem cells. Besides this, the cell therapy is rapidly bringing good advancements in the healthcare system, intending to restore and possibly replace injured tissue, as well as organs, and ultimately restore the functional capacity of the body.2,10,11

The stem cells can be obtained from various sources of Adult (Adult body tissues), Embryonic (Embryos), Mesenchyma (Connective tissue or stroma), and Induced pluripotent stem [ips] cells (Skin cells or tissue-specific cells).3,68,1215

Due to various stem cells cellular characteristics, the therapeutic clinical possibilities of stem-cell-based treatment are considered promising. These cells can regrow and restore various types of body tissues, for this reason, they are recognized as precursor cells to all kinds of cells.15 The following are the distinguishing features: 1. Self-renewal- Divide without distinction to generate an infinite supply, 2. Multi-potency- One mature cell may distinguish more than one, 3. Pluripotency- Create all sorts of cells except for embryonic membrane cells, 4. Toti- potency- Produce various sorts of cells, including embryonic stem cells.1,2,6,7,16

Stem cells are essential human cells that really can self-renew and make a distinction into particular mature cell types.3,6 The different types of stem cells are embryonic, induced pluripotent, and adult kind of cell types. They all share the important feature of self-renewal, and the ability to discern themselves. It should be mentioned that, the stem cells are not homogeneous, but instead appear in a progressive order. Totipotent stem cells are the most basic and immature stem cells. The above cells can form a complete embryo and also extra-embryonic tissue. This one-of-a-kind efficiency is only present for a short period, starting with ovum development and completing whenever the embryo achieves the 4 to 8 cell phases. Having followed that, cells that divide until they approach the blastocyst, about which point they end up losing their totipotency and acquire a pluripotent character trait, at which cells can only distinguish through each embryonic germ stack. After a few divisions, the pluripotency character trait starts to fade and the distinguishing ability has become more lineage constrained, where its cells are becoming multipotent, indicating they could only transform into the cells connected to a cell or tissue of origin.10 Many researchers believe that adult stem cells should be used in stem cell therapies.6,17

The stem cells can be transformed into a wide range of specialized functional cell types.3,18 In response to injury or maturation, those same stem cells can propagate in massive quantities.19 Adult, embryonic, and induced pluripotent stem cells are examples of stem cell-based therapies.14,15,1921 The stem cells, due to their capability to distinguish the specific cell types requisite for a diseased tissue regeneration, can provide an effective solution, while tissue and organ transplantation are considered necessary.10 The sophistication of stem cell-based treatment interventions, on the other hand, probably leads researchers to seek stable, credible, and readily available stem cell sources capable of converting into numerous lineages. As an outcome, it is critical to exercise caution when selecting the type of stem cells to be used in therapeutic trials.12,14,22

Only with the explosive growth of basic stem cell research in recent years, the comparatively recent study sector of Translational Research had also grown exponentially, starting to build on major research knowledge and insight to advance new therapies. Once the necessary regulatory clearances have been obtained, the clinical translation process can start. Translational research is important because it acts as a filtration system, ensuring that only safe and effective therapeutic approaches start making it to the clinic.23 Recent research illustrating, the successful application of stem cell transplantation to patient populations suggests that, such restorative approaches have been used to address a wide variety of complicated ailments of future concerns.19,24

Currently, clinical trials are available for a variety of stem cell-based treatments based on adult stem cells. To date, the WHO International Clinical Experiments Registration process has recorded more than 3000 experiments involved based on adult stem cells. Furthermore, preliminary trials involving novel and intriguing pluripotent stem cell therapies have been registered. These studies findings will assist the ability to comprehend and the timeframes required to obtain effective treatments and it will contribute to a better knowledge of the different disorders or abnormalities.10

The role of stem cells in modern medicine is vital, both for their widespread application in basic research and for the opportunities they provide for developing new therapeutic strategies in clinical practice.6,16 In recent times, the number of studies involving stem cells has expanded tremendously. Globally, thousands of studies claiming to use stem cells in experimental therapies have now been in the investigation field. This may give the impression that such treatments have already been shown to be extremely effective in the context of healthcare. Despite some promising results, the vast majority of stem cell-based therapeutic applications are still in the experimental stage itself.6,25

The stem cells are a valuable resource for understanding organogenesis as well as the bodys continual regenerative capacity. These cells have brought up enormous anticipations among doctors, investigators, patients, and the public at large because of their ability to distinguish into a variety of cell types.25 These cells are necessary for living beings for a variety of reasons and can play a distinguishable role. Several stem cells can play all cell types roles, and when stimulated effectively, they can also repair damaged tissue. This capability has the potential to save lives as well as treat human injuries and tissue destruction. Moreover, different kinds of stem cells could be used for several purposes, including tissue formation, cell deficiency therapeutic interventions, and stem cell donation or retrieval.3,6,26

New research demonstrating that the successful application of stem cell treatments to patients has expressed hope that such regenerative strategies might very well one day is being used to address a wide variety of problematic ailments. Furthermore, clinical trials incorporating stem cell-based therapeutics have advanced at an alarming rate in recent years. Some of these studies had a significant impact on a wide range of medical conditions.10 As a regenerative medicine strategy, cell-based treatment is widely regarded as the most fascinating field of study in advanced science and medicine. Such technological innovation paves the way for an infinite number of transformational and potentially curable solutions to some of humanitys most pressing survival issues. Moreover, it is gradually becoming the next major concern in medical services.11

Modern data, which shows that the successful stem cell transplantation in beneficiaries has raised hopes on the certain rejuvenating approaches, will one day be used to treat many different types of challenging chronic conditions.24 Preliminary data from highly innovative investigations have documented that the prospective advancement of stem cells provides a wide range of life-threatening ailments that have so far eluded current medical therapy.2,10,11 Furthermore, clinical trials involving stem cell-based therapies have advanced at an unprecedented rate. Many of these studies had a significant impact on various disorders.19 Despite the increasing significance of articles concerning viable stem cell-based treatments, the vast majority of clinical experiments have still yet to receive full authorization for stem cell treatments confirmation.11,12,27

Even though the first case of AIDS were noted nearly 27 years ago, and the etiologic agent was noticed 25 years ago, still for the effective control of the AIDS pandemic continues to remain elusive.28 The HIV epidemic started in 1981 when a new virus syndrome defined by a weakened immune system was revealed in human populations across the globe. AIDS showed up to have a substantial reduction in CD4+ cell counts and also elevated B-cell multiplication.15,2831

The agent that causes AIDS, later named HIV, is a retroviral disease with a genomic structural system made up of 2 identical single-stranded RNA particles.3234 According to the Centres for Disease Control and Prevention, with over 1.1 million Americans are presently infected with the virus.31 Compromised immune processes in HIV and AIDS, as well as partial immune restoration, barriers are confirmed for HIV disease eradication. Innovative developmental strategies are essential to maximizing virus protection and enabling the host immune response to eliminate the virus.35

The progression of HIV infection in humans is divided into the following stages of acute infection, chronic infection, and AIDS.15,36 During the acute infection phase, the circulation has a high viral replication, is extremely infectious, that may or may not demonstrate flu-like clinical signs. In the chronic stage, the viral load is lesser than in the acute stage, and individuals are still infectious but may be symptomless. The patient has come to the end stage of AIDS whenever the CD4+ cell count begins to fall below 200 cells/mm or even when opportunistic infections are advanced.15,36

There are currently two types of HIV isolated HIV-1 and HIV-2.15,37,38 However, HIV-1 is the most common cause of AIDS throughout the world, while HIV-2 is only found in a few areas of an African country. Although both virions can cause AIDS, HIV-2 infection is much more likely to occur in central nervous system disorder.15 Besides this, HIV-2 seems to be less infectious than HIV-1, and HIV-2 infection induces AIDS to develop more slowly. Even though both HIV-1 and HIV-2 have a comparable genetic structure comprised of group-specific antigen, polymerase, and envelope genes, their genome organizational structures are differed.15,3739

HIV infiltrates immune cell types, CD4+ T cell types, and monocytes, resulting in a drop in T-cell counts below a critical level and the failure of cell-mediated immune function.15,40 The glycoprotein (gp120) observed in the virion envelope comes into contact with the CD4 particle with high affinity, allowing HIV to infect T cells. By interacting with their co-receptors, CXCR4 and CCR5, the virus infiltrates T cells and monocytes. The retrovirus uses reverse transcriptase to convert its RNA into DNA after attaching it to and entering the host cell. These newly replicated DNA copies then exit the host cell and infect other cells.15,40,41

HIV-1 is a retrovirus and belongs to a subset of retroviruses known as lentiviruses.38,42 Infection is the most common global health concern around the world.15 It has destroyed the millions of peoples health and continues to wreak havoc on the individual health of millions more. The pandemic of HIV-1 is the most devastating plague in the history of humans, as well as a significant challenge in the areas of medicine, public health, and biological science of research activities.34,43 Antiretroviral therapy is the only treatment that is commonly used. This is not a curative treatment; it must be used for the rest of ones life.15 Although antiretroviral therapy has reduced significantly HIV intensity and transmission, the virus has not been eradicated, and its continued presence can lead to additional health issues.44

Infection with the human immunodeficiency virus necessitates entry into target cells, such as through adhesion of the viral envelope to CD4 receptor sites.43 Cellular antiviral responses fail to eliminate the virus, resulting in a gradual depletion of CD4+ T cells and, finally, a severely compromised immune functioning system. Unfortunately, there is no cure for the virus that destroys immunity.4447 In advanced HIV infection, memory T-cell depletion primarily affects cellular and adaptive immune responses, with a minor impact on innate immune responses.48 Globally, 37.7 million people were living with HIV in 2020, and with 1.5 million individuals are infected with the virus.49 The advancement of stem cell therapy and the conduct of implemented clinical trials have revealed that stem cell treatment has high hopes for a range of medical conditions and implementations.15

Stem cell treatment has shown impressive outcomes in HIV management and has the potential to have significant implications for HIV treatment and prevention in the future. In HIV patients, stem cell therapy helps to suppress the viral load even while enabling antiretroviral regimens to be tapered. Interestingly, this practice led to a significant improvement in procedure outcomes soon after starting antiretroviral treatment.15 Stem cell transplantation can alleviate a wide variety of diseases that are currently incurable. They could also be used to create a novel anti-infection therapy strategic plan and to enhance the treatment of immunologic conditions such as HIV infection. HIV wreaks havoc on immune system cells.30,50

The virus infects and replicates within T-helper cells (T-cells), which are white immune system cells. T-cells are also referred to as CD4 cells. HIV weakens a persons immune system over time by pulverizing more CD4 cells and multiplying itself. More pertinently, if the individual has been unable to obtain anti-retroviral medicine, he will progressively fail to control the infectious disease and illnesses.3,15,42

Despite 36 years of scientific research, investigators are still trying to cure human HIV and its potential problem, AIDS.3,5153 HIV continues to face unconquerable dangers to human survival. This virus has developed the potential to avoid anti-retroviral therapy and tends to result in victim death.52 Investigators are still looking for effective and all-encompassing treatment for HIV and its complexity, AIDS.54 This massive amount of data revealed potential AIDS treatment targets.55 Thousands of research projects have yielded a great deal of information on the elusive AIDS life cycle to date.5456 These massive amounts of data supplied possible targets for AIDS treatment.33,55,56 In HIV-infected patients, using stem cell therapy can augment the process of keeping the viral load stagnant by permitting antiretroviral regimens to be tapered.15

Overall, stem cell-based strategies for HIV and AIDS treatment have recently emerged and have become a key area of research. Ideally, effective stem cell-based therapeutic approaches might have several benefits.30 Clinical studies encompassing stem cell therapy have shown substantial therapeutic effects in the treatment of various autoimmune, degenerative, and genetic problems.15,25 Substantial progress has been developed in the treatment of HIV infection using stem cell-based techniques.30

Successfully treated, clinical studies have shown that total tissue recovery is feasible.15,57 In the early 1980s, the first stem cell transplants were accomplished on HIV-positive patients who were unsure of their viral disease. Following the above preliminary aspects, many HIV-positive patients with concurrent malignant tumours or other hematologic disorders underwent allogeneic stem cell transplantation around the world.42 After ART became a common treatment option for patients,58,59 the procedures prognosis improved dramatically. In addition, a retrospective study of 111 HIV+ transplant patients demonstrated a mildly lower overall survivorship performance in comparison to an HIV-uninfected comparison group.60

Earlier, the primary problem for people living with HIV and AIDS was immunodeficiency caused by a loss of productive T-cells. Some clinicians intended to replenish lost lymphocytes through adoptive cell transplants in the initial days before efficacious antiretroviral therapy options were available. Immunologically, it is relatively simple in an isogeneic condition, as illustrated on HIV-positive individuals with just a correlating identical twin who received T-lymphocytes and stem cell transfusions to rebuild the weak immune status of the patient.60 Cell therapy transfusion may be used to remove resting virion genomes from CD4+ immune cells and macrophages mostly through genome-editing or cytotoxic anti-viral cells.15,60 Cell technology and stem cell biological reprogramming developments have made a significant contribution to novel strategies that may give confidence to HIV healing process.3 However, human embryonic stem cells can be distinguished into significant HIV target cells, according to several research findings.30,61,62

Initially, stem cell transplantation was believed to influence the clinical significance of HIV infection, but viral regulation was not accomplished in the discipline. Moreover, improvements in stem cell transplants utilizing synthetic or natural resistant cell resources, in combination with novel genetic manipulative tactics or the advancement of cytotoxic anti-HIV effector cells, have significantly accelerated this sector of HIV cell management.60 Multiple techniques are being introduced to overcome HIV, either through protecting cells from infectious disease or by continuing to increase immune responses to the viral infection.30 The various methods are as follows: Bone marrow stem cells Therapies, Autologous stem cell transplantations, Hematopoietic stem cell transplantation, Genetical modifications of Hematopoietic stem cells (HSCT), HSCT and HAART therapeutic approach, Human umbilical cord mesenchymal stem cell transplantation, Mesenchymal stem/stromal cells (MSCs) applications, CCR5 Delta32/Delta32 Stem-Cell Transplantation, CRISPR and stem cell applications, Induced Pluripotent Stem Cells applications.

According to the findings, circulating replicative HIV remains the most significant threat to effective AIDS therapy. As a result, a method for conferring resistance to circulating HIV particles is required. The effective viral burden in the human body would be significantly reduced if it were possible to defeat reproducing HIV particles.43,44 For the treatment of AIDS, a restorative approach that relies on bone marrow stem cells has been suggested.52 The proposed treatment method captures and eventually destroys circulating HIVs using receptor-integrated red blood cells. Red blood cell membranes can be equipped with the CD4 receptor and the C-C chemokine receptor type 5 and C-X-C chemokine receptor type 4 co-receptors, which will selectively bind circulating HIV particles.15,30,32,33,43,44,46,6365

The term autologous pertains to blood-forming stem cells obtained from the patient for use as a source of fresh blood cells followed by high-dose chemotherapeutic agents.66 Lymphoma is still the biggest cause of mortality in HIV patients. Autologous stem cell recovery or transplantation with high-dose treatments has long been supported as a treatment for certain types of cancer in HIV-negative patients, including leukaemia and lymphoma. Individuals over the age of 65, as well as those with health problems such as HIV, were excluded from initial transfusion experiments. Moreover, the treatment regimen mortality of transplantation has also been reduced significantly due to its use of peripheral blood stem cells rather than bone marrow and the use of newer marginal conditioning therapeutic strategies. HIV-infected clients may be able to utilize enough stem cells for an autologous transplant advancement in HIV management. High-dose Autologous stem cell transplant (ASCT) treatments are better than conventional treatment in people with relapsed non-Hodgkin lymphoma, according to randomized trial evidence. Similarly, studies on HIV-negative people with Hodgkin Lymphoma have shown that ASCT would provide patients with repetitive illness with long-term progression-free survival.66,67 Even so, the clinical trial on Allogeneic Hematopoietic Cell Transplant for HIV Patients with Hematologic Malignancies report was explained as, the cell-associated HIV DNA and inducible infectious virus were not detectable in the blood of patients who attained complete chimerism.68

The study on long-term multilineage engraftment of autologous genome-edited hematopoietic stem cells in nonhuman primates report findings was Genome editing in hematopoietic stem and progenitor cells (HSPCs) is a potential innovative approach for the treatment of numerous human disorders. This report shows that genome-edited HSPCs engraft and contribute to multilineage repopulation following autologous transplantation in a clinically relevant large animal model, which is an important step toward developing stem cell-based genome-editing therapeutics for HIV and possibly other illnesses.69

Research on comprehensive virologic and immune interpretation in an HIV-infected participant again just after allogeneic transfusion and analytical interruption of antiretroviral treatment findings are the instance of HIV-1 cure having followed allogeneic stem cell transplantation (allo-SCT), resulting allo-SCTs in HIV-1 positive participants have failed to cure the disease. It describes adjustments in the HIV reservoir in a single chronically HIV-infected client who had undergone allo-SCT for acute lymphoblastic leukaemia treatment and was obtaining suppressive antiretroviral treatment.

To estimate the size of the HIV-1 reservoir and describe viral phylogenetic and phenotypic modifications in immune cells, the investigators just used leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) from a 55-year-old man with chronic HIV infection prior and after allo-SCT. Once HIV-1 was found to be unrecognizable by numerous tests, including the PCR measurement techniques both of overall and fully integrated HIV-1 DNA, recompilation virus precise measurement by significant cell input quantifiable viral outgrowth assay, and in situ hybridization of intestine tissue, the client accepted to an analytic treatment interruption (ATI) with recurrent clinical observing on day 784 post-transplantation. He continued to remain aviremic off ART until ATI day 288, once a reduced virus rebound of 60 HIV-1 copies/mL resulted, which expanded to 1640 HIV-1 copies/mL five days later, urging ART reinitiation. Rebounding serum HIV-1 action sequences were phylogenetically distinguishable from pro-viral HIV-1 DNA discovered in circulating PBMCs before transplantation. It was indicated that allo-SCT tends to result in significant reductions in the magnitude of the HIV-1 reservoir and a >9-month ART-free cessation from HIV-1 multiplication.34

The Impact of HIV Infection on Transplant Outcomes after Autologous Peripheral Blood Stem Cell Transplantation: A Retrospective Study of Japanese Registry Data reported as ASCT is a successful treatment option for HIV-positive patients with non-Hodgkin lymphoma and multiple myeloma (MM). HIV infection was associated with an increased risk of overall mortality and relapse after ASCT for NHL in a study population.70

The procedure of delivering hematopoietic stem cells mostly through intravenous infusion to restore normal haematopoiesis or treat cancer is known as hematopoietic stem cell transplantation.71 There has recently been a rise in the desire to develop strategies for treating HIV/AIDS diseases employing human hematopoietic stem cells,30 along with this Hutter and Zaia were evaluated the background of Haematopoietic stem cell transplantation (HSCT) in HIV-infected individuals.42

Attempts to use HSCT as a technique for immunologic restoration in AIDS patients or as a therapeutic intervention for malignant tumours were initially insufficient. Regretfully, in the absence of sufficient ART, HSCT seemed to have no impact on the evolution of HIV infection, and the majority of the patients ended up dead of rapidly deteriorating immunosuppression or reoccurring lymphoma or leukaemia. A specific instance report described how an un-associated, matched donor supplied allogeneic HSCT to a patient with refractory lymphoma. The virus was unrecognizable by isolating or PCR of peripheral blood mononuclear cells commencing on day 32 after transplantation. Although HIV-1 was unrecognizable by cultural environment or PCR of several tissues examined at mortem, the patient died of recurring lymphoma on day 47. Another client who obtained both allogeneic HSCT and zidovudine had similar results, with HIV-1 becoming unnoticeable in the blood by PCR analysis. In some other particular instances, a 25-year-old woman with AIDS who obtained an allogeneic HSCT from a corresponding, unfamiliar donor after controlling with busulfan and cyclophosphamide and ART with zidovudine and IFN-2 regimen continued to live for 10 months before falling victim to adult respiratory distress. However, PCR testing of autopsy tissues revealed that they were HIV-1 negative.72

Recent research discovered significant progress towards the clinical application of stem cell-based HIV therapeutic interventions, principally illustrating the opportunity to effectively undertake a large-scale phase two HSC-based gene therapy experiment. In this investigation, the research team used autologous adult HSCs that had been transduced to a retroviral vector that usually contains a tat-vpr-specific anti-HIV ribozyme to develop cells that were less vulnerable to productive infection,73 whereas vector-containing cells have been discovered for extended periods (more than 100 weeks in most people) and CD4+ T cell gets counted were significantly high within anti-HIV ribozyme treating people group compared with the placebo group, the impacts on viral loads were minimal. The studys success, even so, is based on the realization that a stem cell-based strategy like this is being used as a more conventional and efficacious therapeutic approach.30 Some other latest clinical studies used a multi-pronged RNA-based strategic plan which included a CCR5-targeted ribozyme, an shRNA targeting tat/rev transcripts, and a TAR segment decoy.74

These crucial research findings are explained on lentiviral-based gene therapy vectors that can genetically manipulate both dividing and non-dividing HSCs and are less likely to cause cellular changes than murine retro-viral-based vectors. Long-term engraftment and multipotential haematopoiesis have been demonstrated in vector-containing and expressing cells, according to the researchers. Whereas the antiviral effectiveness was not reviewed, the results demonstrate the strategys protection, which helps to expand well for the possibility of a lentiviral-based approach in the upcoming years.30

A further approach, with a different emphasis, has been started up in the hopes of trying to direct immune function to target specific HIV to overcome barriers to attempting to clear the virus from the patient's body. These strategies use gene treatment innovations on peripheral blood cells to biologically modify cells so that they assert a receptor or chimeric particle that enables them to especially target a specific viral antigen,75 deception of HIV-infected peoples peripheral blood T cells raises issues to be addressed, such as the effects of ongoing HIV infection and ex vivo modification on the capabilities and lifetime of peripheral blood cells. Further to that, the above genetically manipulated cells would demonstrate their endogenous T cell receptors, and the representation of the newly introduced receptor could outcome in cross-receptor pairing, resulting in self-reactive T cells. Most of these deficiencies could be countered by enabling specific developmental strategies to take place that can start generating huge numbers of HIV-specific cells in a renewable, consistent way that can restore defective natural immune activity against HIV.30

One strategy being recognized is the application of B cells obtained from HSCs to demonstrate anti-HIV neutralizing specific antibodies. While animal studies have shown that neutralizing antibodies could protect against infection, and extensively neutralizing antibodies have been noticed in some HIV-infected persons, safety from a single engineered antibody might be exceptional.76,77 Realizing antibody binding and virus neutralization may assist in the development of chimeric receptors or single-chain therapeutic antibodies with recognition domains for other techniques that identify cellular immunity against HIV-infected cells.78,79 Thereby, genetically modifying HSCs to generate B cells that produce neutralizing anti-HIV specific antibodies, or engineering HSCs to enable multipotential haematopoiesis of cells that express a chimeric cellular receptor usually contains an antibody recognition domain, indicate one arm of an HSC-based engineered immunity process.30

A further technique of using HSCs that were genetically altered with molecularly cloned T-cell receptors or chimeric molecules particular to HIV to yield antigen-specific T cells. The basic difference in this strategy is that the cells produced from HSCs after standard advancement in the bone marrow and thymus are made subject to normal central tolerance modalities and are antigen-specific naive cells, and therefore do not have the ex-vivo manipulation and impaired functioning or exhaustion problems that other external cell modification methods would have. In this context, the latest actual evidence research using a molecularly cloned T cell receptor particular to an HIV-1 Gag epitope in the aspect of HLA-A*0201 revealed that HSC altered in this ability can progress into fully functioning, mature HIV specialized CD8+ T cells in human thymic tissue that conveys the acceptable constrained HLA-A*0201 particles.80 This explores the possibility of genetically engineering HSCs with a molecularly cloned receptor and signifies a step toward a better understanding and application of initiated T cell responses, which would probably result in the eradication of HIV infection from the body, similar to the natural immune function of other virus infections and pathogenic organisms.30

In an allogeneic transplantation, donor stem cells replace the patients cells.66 Allogeneic hematopoietic stem cell transplantation (HSCT) has appeared as one of the most potent treatment possibilities for many people who suffer from hemopoietic system carcinomas and non-malignant ailments.81 Both HIV-cured people have received HSCT utilizing CCR5 132 donor cells.82,83 This implies that HIV eradication necessitates a decrease in the viral reservoir through the myeloablative procedures,8486 Having followed that, immune rebuilding with HIV-resistant cells was carried out to prevent re-infection.45 The possibility of adoptive transfer of ex vivo-grown, virus-specific T-cells to prevent and control infectious diseases (eg, Cytomegalovirus and EBV) in immunocompromised patients helps to make adoptive T-cell treatment a feasible strategy to inhibit HIV rebound having followed HSCT.81,87,88

The Engineered Zinc Finger Protein Targeting 2LTR Inhibits HIV Integration in Hematopoietic Stem and Progenitor Cell-Derived Macrophages: In Vitro Study, the researchers investigated the efficacy and safety of 2LTRZFP in human CD34+ HSPCs. Researchers used a lentiviral vector to transduce 2LTRZFP with the mCherry tag (2LTRZFPmCherry) into human CD34+ HSPCs. The study findings suggest that the anti-HIV-1 integrase scaffold is an enticing antiviral molecule that could be utilised in human CD34+ HSPC-based gene therapy for AIDS patients.89

The fundamental element of HIV management is stem cell genetic modification, which involves genetically enhanced patient-derived stem cells to overcome HIV infection. In this sector, numerous experimental studies, in vitro as well as in vivo examinations, and positive outcomes for AIDS patients have been conducted.65,74 Genetic engineering for HIV-infected individuals can provide a once-only intervention that minimizes viral load, restores the immune system, and minimizes the accumulated toxicities concerned with highly active antiretroviral therapy (HAART).73 HSCs can be genetically altered, permitting for the addition of exogenous components to the progeny that protects them from direct infectious disease and/or enables them to target a specific antigen. Besides that, HSC-based strategies can enhance multilineage hemopoietic advancement by re-establishing several arms of the immune function. Eventually, as HSCs can be produced autologously, immunologic tolerance is typically high, enabling effective engraftment and subsequent distinction into the fully functioning mature hematopoietic cells.30

The utilization of human HSCs to rebuild the immune function in HIV disease is one application that tries to preserve newly formed cells from HIV infection, while another attempts to develop immune cells that attack HIV infected cells. While each initiative has many different aspects at the moment, they represent huge attention to HIV/AIDS therapies that, most likely when integrated with the other therapeutic approaches, would result in the body trying to overcome the obstacles needed for the virus to be effectively cleaned up.30

While HSC transplantation technique and processes are not accurately novel, as they are commonly and effectively used to address a wide variety of haematological diseases and malignant neoplasms,90 trying to combine them with a gene therapeutic strategy represents a unique and possibly potent therapeutic approach for HIV and AIDS-related ailments. As the results of HIV-infected patients who obtained autologous HSCT continued to improve, there was growing interest in genetically altered stem cells that were tolerant to HIV disease. Multiple logistical challenges have impeded the advancement of genetically modified hematopoietic stem cells as a conceivable therapeutic option for HIV/AIDS.72,73

UCLAs Eli and Edythe Broad Center for Restorative Medicine and Stem Cell Studies is one bit closer to constructing an instrument to arm the bodys immune system to attack and defeat HIV. Dr. Kitchen et al are the first ones to disclose the use of a chimeric antigen receptor (CAR), a genetically manipulated molecule, in blood-forming stem cells. In the experiment, the research team introduced a CAR gene into blood-forming stem cells, which were then moved into HIV-infected mice that had been genetically programmed. The scientists found that CAR-carrying blood stem cells efficiently transformed into fully functioning T cells that have the ability to kill HIV-infected cells in mice. The outcome was an 80-to-95 percentage reduction in HIV levels, suggesting that stem-cell-based genetic engineering with a CAR might be a viable and effective approach for treating HIV infection among humans. The CAR initiative, according to Dr. Kitchen, is much more able to adapt and ultimately more efficient, which can conceivably be used by others. If any further experiment showcases keep promising, the scientists expect that a practice based on their strategy will be accessible for clinical development within the next 510 years.91

HSCT and HAART therapeutic approaches in treating HIV/AIDS as the emergence of highly active antiretroviral therapy (HAART) in the 1990s improved survival rates of HIV infection, leading to a major dramatic drop in the occurrence of AIDS and AIDS-related mortalities. As an outcome, there is much less involvement with using HSCT as a therapy for HIV infection.28,33,43,67,86

A randomized clinical trial of human umbilical cord mesenchymal stem cell transplant among HIV/AIDS immunological non responders investigation, the researchers examined the clinical efficacy of transfusion of human umbilical cord mesenchymal stem cells (hUC-MSC) for immunological non-responder clients with long-term HIV disease who have an unmet medical need in the aspect of effective antiretroviral therapy. From May 2013 to March 2016, 72 HIV-infected participants were admitted in this stage of the randomized, double-blind, multi-center, placebo-controlled dose-determination investigation. They were either given a high dose of hUC-MSC of 1.5106/kg body weight as well as small doses of hUC-MSC of 0.5106/kg body weight, or a placebo application. During the 96-week follow-up experiment, interventional and immunological character traits were analysed. They found that hUC-MSC therapy was both safe and efficacious among humans. There was a significant rise in CD4+ T counts after 48 weeks of treatment in both the high-dose (P 0.001) and low-dose (P 0.001) groups, but no changes in the comparison group.92

One interesting invention made by a team of UC Davis investigators is the recognition of a particular form of stem cell that can minimize the quantity of the virus that tends to cause AIDS, thus dramatically increasing the bodys antiviral immune activity. Mesenchymal stem/stromal cells (MSCs) furnish an incredible opportunity for a creative and innovative, multi-pronged HIV cure strategic plan by augmenting prevailing HIV potential treatments. Even while no antivirals have been used, MSCs have been able to increase the hosts antiviral responses. MSC therapeutic approaches require specialized delivery systems and good cell quality regulation. The studys findings lay the proper scientific foundation for future research into MSC in the ongoing treatment of HIV and other contagious diseases in the clinical organization.35

Infection with HIV-1 necessitates the existence of both specific receptors and a chemokine receptor, particularly chemokine receptor 5 (CCR5).46 Resistance to HIV-1 infection is attained by homozygozygozity for a 32-bp removal in the CCR5 allele.93 In this investigation, stem cells were transplanted in a patient with severe myeloid leukaemia and HIV-1 infection from a donor who was homozygous to Chemokine receptor 5 delta 32. The client seemed to have no viral relapses after 20 months of transplantation and attempting to stop antiretroviral medicine. This finding highlights the essential role that CCR5 tries to play in HIV-1 infection maintenance.86

In comparison, additional HIV-1-infected people who have received allogeneic stem cell transplants with cells from CCR5 truly wild donors did not have long-term relapses from HIV-1 rebound, with 2 of these patients trying to report viral reoccurrence 12 as well as 32 weeks after analytic treatment interruption, respectively. Among these 2 patients, allogeneic stem cell transplantation probably reduced but did not eliminate latently HIV-infected cells, enabling persistent viral reservoirs to activate viral rebound. This viewpoint may not rule out the potential that allogeneic hematopoietic stem cell transplantation might result in a much more comprehensive or near-complete elimination of viral reservoirs, enabling long-term drug-free relapse of HIV-1 infection in some contexts.84 As just one report demonstrated a decade earlier, a curative treatment for HIV-1 remained elusive. The Berlin Patient has undergone 2 allogeneic hematopoietic stem cell transplantations to cure his acute myeloid leukaemia utilizing a potential donor with a homozygous genetic mutation in HIV coreceptor CCR5 (CCR532/32).15,34,46,64,65,72,82,84,86,9496 Other similar studies with CCR5 receptor targets are as follows: Automated production of CCR5-negative CD4+-T cells in a GMP compatible, clinical scale for treatment of HIV-positive patients,97 Mechanistic Models Predict Efficacy of CCR5-Deficient Stem Cell Transplants in HIV Patient Populations,98 Conditional suicidal gene with CCR5 knockout.99

Clustered regularly interspaced short palindromic repeats CRISPR/Cas9 is a promising gene editing approach that can edit genes for gain-of-function or loss-of-function mutations in order to address genetic abnormalities. Despite the fact that other gene editing techniques exist, CRISPR/Cas9 is the most reliable and efficient proven method for gene rectification.100103

Genome engineering employing CRISPR/Cas has proven to be a strong method for quickly and accurately changing specific genomic sequences. The rise of innovative haematopoiesis research tools to examine the complexity of hematopoietic stem cell (HSC) biology has been fuelled by considerable advancements in CRISPR technology over the last five years. High-throughput CRISPR screenings using many new flavours of Cas and sequential and/or functional outcomes, in specific, have become more effective and practical.104,105

The power of the CRISPR/Cas system is that it can specifically and efficiently target sequences in the genome with just a single synthetic guide RNA (sgRNA) and a single protein. Cas9 is directed to the specific DNA sequence by the sgRNA, which causes double stranded breaks and activates the cells DNA repair processes. Non-homologous end joining can cause insertiondeletion (indel) substitutions at the target location, whereas homology-directed repair can use a template DNA to insert new genetic material.104,106

The possibility for CRISPR/Cas9 to be used in the hematopoietic system was emphasised as pretty shortly after it was initiated as a new genome editing method.106,107 The efficiency with which CRISPR-mediated alteration can be used to evaluate hematopoietic stem/progenitor and mature cell function via transplantation. As a result, hematopoietic research has significantly advanced with the implementation of these technologies. Whilst single-gene CRISPR/Cas9 programming is a significant tool for testing gene function in primary hematopoietic cells, high-throughput screenings potentially offer CRISPR/Cas9 an even greater advantage in hematopoietic research.104

While understanding human haematological disorders requires the ability to mimic diseases, the ultimate goal is to transfer this innovation into therapies. Despite significant advancements in CRISPR technology, there are still barriers to overcome before CRISPR/Cas9 can be used effectively and safely in humans. CRISPR has also been used to target CCR5 in CD34+ HSPCs in an effort to make immune cells resistant to HIV infection, as CCR5 is an important coreceptor for HIV infection.104

CRISPR is a modern genome editing technique that could be used to treat immunological illnesses including HIV. The utilization of CRISPR in stem cells for HIV-related investigation, on the other end, was ineffective, and much of the experiment was done in vivo. The new research idea is about increasing CRISPR-editing efficiencies in stem cell transplantation for HIV treatment, as well as its future perspective. The possible genes that enhance HIV resistance and stem cell engraftment should be explored more in the future studies. To strengthen HIV therapy or resistance, double knockout and knock-in approaches must be used to build a positive engraftment. In the future, CRISPR/SaCas9 and Ribonucleoprotein (RNP) administration should be explored in the further investigations.108 As well as some different title studies were explained the effectiveness of the CRISPR gene editing technology on the management of HIV/AIDS including: CRISPR view of hematopoietic stem cells: Moving innovative bioengineering into the clinic,104 CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukaemia,109 Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice,110 Extinction of all infectious HIV in cell culture by the CRISPR-Cas12a system with only a single crRNA,111 HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells,112 CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination,113 RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection,114 CRISPR/Cas9 Ablation of Integrated HIV-1 Accumulates Pro viral DNA Circles with Reformed Long Terminal Repeats,115 CRISPR-Cas9-mediated gene disruption of HIV-1 co-receptors confers broad resistance to infection in human T cells and humanized mice,116 Inhibition of HIV-1 infection of primary CD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR/Cas9,117 Transient CRISPR-Cas Treatment Can Prevent Reactivation of HIV-1 Replication in a Latently Infected T-Cell Line,118 CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection,119 CRISPR/Cas9-Mediated CCR5 Ablation in Human Hematopoietic Stem/Progenitor Cells Confers HIV-1 Resistance In Vivo.109

Induced pluripotent stem cells (iPSCs) have significantly advanced the field of regenerative medicine by allowing the generation of patient-specific pluripotent stem cells from adult individuals. The progress of iPSCs for HIV treatment has the potential to generate a continuous supply of therapeutic cells for transplantation into HIV-infected patients. The title of the study is reported on Generation of HIV-1 Resistant and Functional Macrophages from Hematopoietic Stem Cellderived Induced Pluripotent Stem Cells. In this investigation, researchers used human hematopoietic stem cells (HSCs) to produce anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into constantly growing iPSC lines using 4 reprogramming factors and a combination anti-HIV lentiviral vector comprising a CCR5 shRNA and a human/rhesus chimeric TRIM5 gene. After directing the anti-HIV iPSCs toward the hematopoietic lineage, a large number of colony-forming CD133+ HSCs were acquired. These cells were distinguished further into functional end-stage macrophages with a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages displayed good protection against HIV-1 infection. Researchers have clearly shown how iPSCs can establish into HIV-1 resistant immune cells and explain their prospective use in HIV gene and cellular therapies.120

Some other similar titles of the studies reported on the effectiveness of IPSCs on HIV/AIDS managements are as follows: Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA,121 Generation of HIV-1-infected patients gene-edited induced pluripotent stem cells using feeder-free culture conditions,122 A High-Throughput Method as a Diagnostic Tool for HIV Detection in Patient-Specific Induced Pluripotent Stem Cells Generated by Different Reprogramming Methods,123 Genetically edited CD34+ cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells,124 Engineered induced-pluripotent stem cell-derived monocyte extracellular vesicles alter inflammation in HIV humanized mice,125 Sustainable Antiviral Efficacy of Rejuvenated HIV-Specific Cytotoxic T Lymphocytes Generated from Induced Pluripotent Stem Cells.126

Recently, one HIV patient appeared to be virus-free after having undergone a stem-cell transfusion in which their WBCs were changed with HIV-resistant variations.84 Timothy Ray Brown also noted as the Berlin patient, who is still virus-free, was the first individual to undertake stem-cell transplantation a decade earlier. The most recent patient, like Brown, had a type of leukaemia that was vulnerable to chemo treatments. They required a bone marrow transplantation, which involved removing their blood cells and replacing them with stem cells from a donor cell.5,31,34,41,127130 Rather than simply choosing a suitable donor, Ravindra Gupta et al chose one who already had 2 copies of a mutant within the CCR5 gene,128,131 which provides resistance to HIV infection.3

Additionally, this gene encodes for a specific receptor of white blood cells that are assisted in the bodys immunological responses. The transplant, according to Guptas team, completely replaced the clients White cells with HIV-resistant forms.41,83 Cells in the patients blood disrupted expressing the CCR5 receptor, making it unfeasible for the clients form of HIV to infect the above cells again. The scientists determined that the virus had been cleared from the patients blood after the transplantation. Besides that, after 16 months, the client has withdrawn antiretroviral treatment. The infection was not detected in the most recent follow-up, which occurred 18 months after the treatment was discontinued. Adam, also known as the London patient, was the second person to be cured of HIV as a result of a stem cell transfusion. This discovery is an important step forward in HIV research because it may aid in the detection of potential future therapeutic interventions. It must be noted, but even so, that this is not an extensively used HIV treatment. For HIV-infected patients, antiretroviral drugs have been the foremost therapeutic option.3,31,41,94,129,130 It also encourages many investigators and clinicians to look at the use of stem cells in the treatment of a wide range of serious medical conditions. The reprogramming abilities of stem cells, as well as their accessibility, have created a window of opportunity in medical research. The clinical utility of stem cells is forecast to expand rapidly in the coming years.

On Feb 15, 2022, scientific researchers confirmed that a woman had become the 3rd person in history to be successfully treated for HIV, the virus that causes AIDS, after just receiving a stem-cell transfusion that has used cells from cord blood. Within those transplant recipients, adult hematopoietic stem cells have been used; these are stem cells that eventually develop into all blood cell types, which include white blood cells, these are a vital component of the immune framework. Even so, the woman who had fairly recently been completely cured of HIV infection had a more unique experience than that of the 2 men who were actually cured before her.132

The clients physician, Dr. JingMei Hsu of Weill Cornell Medicine in New York, informed them that, she had been discharged from the hospital just 17 days after her procedure was performed, even with no indications of graft vs host ailment. The woman was HIV-positive but also had acute myeloid leukaemia, a blood cancer of the bone marrow that affects blood-forming cells. She had likely received cord blood as a successful treatment for both her cancer and HIV once her doctors decided on a potential donor well with HIV-blocking gene mutation. Cord blood comprises a high accumulation of hematopoietic stem cells; the blood is obtained during a childs birth and donated by the parents.132

The patients donor was partly nearly matched, and she received stem cells from a close family member to enhance her immune function after the transfusion. The procedure was performed on the woman in August of 2017. She chose to discontinue taking antiretroviral drugs, the standardized HIV intervention, 37 months upon her transfusion. After more than 14 months, there is no evidence of the viral infection or antibodies against it in her blood. Umbilical cord blood, in reality, is much more commonly accessible and simpler to try to match to beneficiaries than bone marrow. Perhaps, some research suggests that the method could be more available to HIV patients than bone marrow transplantation. Nearly 38 million people worldwide are infected with HIV. The potential for using partly matched umbilical cord blood transplantation increases the chances of choosing appropriate suitable donors for these clients considerably.132

It is really exciting to see the earlier terminally ill diseases of being effectively treated. In recent times, there has been a surge of focus on stem cell research.3 Stem cell therapy advancements in inpatient care are receiving a growing amount of attention.20 HIV/AIDS has been and remains a significant health concern around the world. Effective control of the HIV pandemic will necessitate a thorough understanding of the viruss transmission.32

Despite concerns about full compliance and adverse reactions, HAART has demonstrated to be able to succeed and is a sign specifically targeted form of treatment against HIV advancement. As illustrated by the first case of HIV infection relapse attained by bone marrow transplant, anti-HIV HPSC-based stem cell treatment and genotype technology have established a possible future upcoming technique to try to combat HIV/AIDS.

Investigators have conducted experiments with engineering distinct anti-HIV genetic traits trying to target different phases of HIV infection utilizing advanced scientific modalities. In numerous in vivo and in vitro animal studies, HSPCs and successive mature cells were secured from HIV infection by trying to target genetic factors in the infection. Anti-HIV gene engineering of HSPCs is safe and efficacious.15

The number of stem-cell-based research trials has risen in recent years. Thousands of studies claiming to use stem cells in experimental therapies have been registered worldwide. Despite some promising results, the majority of clinical stem cell technologies are still in their early life. These achievements have drawn attention to the possibility of the potential and advancement of various promising stem cell treatments currently in development.11

HIV remains a major danger to humanity. This virus has developed the ability to evade antiretroviral medication, resulting in the death of individuals. Scientists are constantly looking for a treatment for HIV/AIDS that is both effective and efficient.52 The 1st treatments in HIV+ clients were conducted in the early 1980s, even though they were cognizant of their viral disease. Following these early cases, allogeneic SCT was used to treat HIV+ patients with associated cancer or other haematological disorders all over the world. Stem cell transplantation developments have also stimulated the improvement of innovative HIV therapeutic approaches, especially for large goals like eradication and relapse.60

Numerous stem cell therapy progressions have been recognized with autologous and allogeneic hematopoietic stem cell transplantation, as well as umbilical cord blood mesenchymal stem cell transplant in AIDS immunologic non-responders. Whereas this sector continues to advance and distinguishing directives for these cells become much more effective, totipotent stem cells such as hESC and the recently reported induced pluripotent stem cells (iPSC) could be very useful for genetic engineering methods to counter hematopoietic abnormalities such as HIV disease.133135

Immunocompromised people are at a higher risk of catching life-threatening diseases. The perseverance of latently infected cells, which is formed by viral genome inclusion into host cell chromosomes, is a significant challenge in HIV-1 elimination. Stem cell therapy is producing impressive patient outcomes, illustrating not only the broad relevance of these strategies but also the huge potential of cell and gene treatment using adult stem cells and somatic derivative products of pluripotent stem cells (PSCs).

Stem cells have enormous regeneration capacity, and a plethora of interesting therapeutic uses are on the frontier. This is a highly interdisciplinary scientific field. Evolutionary biologists, biological technicians, mechanical engineers, and others that have evolved novel concepts and decided to bring them to medical applications are required to make important contributions. Further to that, recent advancements in several different research areas may contribute to stem cell application forms that are novel. Several hurdles must be conquered, however, in the advancement of stem cells. On the other hand, this discipline appears to be a promising and rapidly expanding research area.

Stem cell-based approaches to HIV treatment resemble an innovative approach to trying to rebuild the ravaged bodys immune system with the utmost goal of eliminating the virus from the body. We will probably see effective experiments from the next new generation of stem cell-based strategies shortly, which will start serving as a base for the further development and use of these techniques in a range of treatment application areas for other chronic diseases.

My immense pleasure was mentioned to family members and friends, who supported and encouraged me in every activity.

There was no funding for this work.

The authors declare that they have no conflicts of interest in relation to this work.

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PROMISING STEM CELL THERAPY IN THE MANAGEMENT OF HIV & AIDS | BTT - Dove Medical Press