Category Archives: Cell Medicine

SAN FRANCISCO and TAIPEI, Taiwan, Sept. 01, 2020 (GLOBE NEWSWIRE) -- Acepodia, a biotechnology company developing next generation solid tumor and blood-based cancer cell therapies, today announced key appointments to its business and clinical development teams. Mark J. Gilbert, M.D., a cell therapy pioneer, joins as senior vice president of Research and Development and will lead early-stage research efforts to advance the companys proprietary, potent and off-the-shelf cell therapies from exploratory development stages into clinical trials. Joseph S. McCracken, D.V.M., an industry veteran with over 25 years of experience in the biopharmaceutical industry, has been appointed as senior vice president of Business Development and will play a key role in driving strategic alliances and partnerships.

Dr. Gilberts decades of experience developing and managing successful oncology portfolios coupled with Dr. McCrackens extensive expertise in pharmaceutical business development operations will be essential for the near- and long-term growth of Acepodia, said Sonny Hsiao, Ph.D., chief executive officer of Acepodia. They are joining at a critical time for the company as we have recently entered clinical trials with our lead NK cell therapy in HER2 solid tumors and we continue to engage with global companies in the development and commercialization of next-generation cell therapies. We welcome them to the senior management team and look forward to their insight and leadership.

Dr. Gilbert added, Acepodias therapeutic approach to overcoming the challenges of treating solid tumors by arming its unique off-the-shelf platform with innovative tumor-targeting mechanisms is very promising. It represents an exciting potential breakthrough in the cell therapy treatment landscape. I look forward to working with the team to help realize this potential by advancing its revolutionary approach.

Dr. McCracken added, I am thrilled to join Acepodia at a pivotal time for the company and look forward to creating new synergies and strategic relationships that deliver value to the company, its partners and its stakeholders, while helping to advance its mission of delivering the next generation of effective cell therapies to patients.

Dr. Gilbert has decades of experience leading strategic drug development and portfolio management in medical oncology for several U.S. biotech and pharmaceutical companies. He was previously the chief medical officer of Juno Therapeutics, where he led the clinical development of its CAR-T cell therapy pipeline. Dr. Gilbert served as vice president and head of global clinical development, therapeutic area oncology at Bayer Schering Pharmaceuticals. Prior to Bayer Schering, he held several executive positions with Berlex Pharmaceuticals and its parent company Schering, AG, most recently as vice president and head of the global medical development group. Dr. Gilbert joined Berlex from Immunex, where his responsibilities included clinical development and medical affairs for Leukine and Mitoxantrone in hematology, oncology, Crohns disease, and multiple sclerosis. Dr. Gilbert received a B.S. in Biochemistry from the University of Iowa and his M.D. from the University of Iowa Medical School. He trained in internal medicine, infectious disease and medical oncology at the University of California, San Francisco, and the University of Washington, respectively. Prior to his executive positions in biotech and oncology companies, Dr. Gilbert was a faculty member at the Fred Hutchinson Cancer Research Center and the University of Washington and trained in the laboratory of Dr. Phil Greenberg, one of scientific co-founders of Juno Therapeutics.

Dr. McCracken has more than 25 years of experience in research, strategic business development and commercial roles in biotechnology and pharmaceutical companies. He was previously vice president and global head of business development and licensing for Roche Pharma, where he was responsible for Roche Pharmas global in-licensing and out-licensing activities. Prior to joining Roche Pharma, Dr. McCracken held the position of vice president of business development at Genentech for more than nine years, and previously held similar positions at Aventis Pharma and Rhone-Poulenc Rorer. Dr. McCracken holds a Bachelor of Science in Microbiology, a Master of Science in Pharmacology and a Doctor of Veterinary Medicine (D.V.M.) from The Ohio State University.

About Acepodia

Acepodia is a privately held biotechnology company focused on eradicating cancers of all types with potent and targeted first-in-class cell therapies. The companys next generation off-the-shelf natural killer (NK) cell therapies are based on a proprietary NK cell line (oNK) that has been selected for its potent anti-tumor activity. Acepodias flexible drug development platform is designed to supercharge oNK cells tumor affinity through both its chimeric antigen receptor technology and its unique ACC (Antibody-Cell Conjugation) technology that links tumor-targeting antibodies to the surface proteins of oNK cells. Its lead product candidate, ACE1702, is the first antibody-conjugated NK cell therapy in clinical development for the treatment of HER2-expressing solid tumors. For more information, visit https://www.acepodia.com.

Acepodia ContactSpike LoAcepodia886 (2) 2697-6100spike@acepodiabio.com

Investor ContactSylvia WheelerWheelhouse Life Science Advisorsswheeler@wheelhouselsa.com

Media ContactMichael Tattory LifeSci Communications1 (646) 751-4362mtattory@lifescicomms.com

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Acepodia Strengthens Management Team with Appointments of Biotech Industry Veterans - GlobeNewswire

DetailsCategory: AntibodiesPublished on Tuesday, 01 September 2020 10:48Hits: 174

Only PD-1/PD-L1 immunotherapy to demonstrate a significant survival benefit and improved response rate in combination with a choice of chemotherapies

LONDON, UK I September 01, 2020 I AstraZenecas Imfinzi (durvalumab) has been approved in the European Union for the 1st-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) in combination with a choice of chemotherapies, etoposide plus either carboplatin or cisplatin.

SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.1,2

The approval by the European Commission was based on positive results from the Phase III CASPIAN trial showing Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit for the 1st-line treatment of patients with ES-SCLC. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2020.

Luis Paz-Ares MD, Ph.D., Chair, Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain and principal investigator in the Phase III CASPIAN trial said: For the first time, patients with extensive-stage small cell lung cancer in Europe will have the option of an immunotherapy combination with cisplatin, a preferred chemotherapy for many European physicians in this setting. Todays approval of Imfinzi provides physicians with an important new 1st-line treatment option that provides significant overall survival benefit with a well-tolerated treatment.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: Imfinzi plus chemotherapy is becoming a new global standard of care for patients with extensive-stage small cell lung cancer, and we are pleased to bring this option to patients in Europe who urgently need it. This is the first immunotherapy regimen to offer both a sustained survival benefit and an improved response rate, as well as a choice of chemotherapies and convenient dosing every four weeks during maintenance.

The CASPIAN trial met the primary endpoint of OS for Imfinzi plus chemotherapy in June 2019, reducing the risk of death by 27% versus chemotherapy alone (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), with median OS of 13.0 months versus 10.3 months for chemotherapy alone. These results were published in The Lancet in 2019.3 Results also showed an increased confirmed objective response rate for Imfinzi plus chemotherapy (68% versus 58% for chemotherapy alone) and that Imfinzi added to chemotherapy delayed the time for disease symptoms to worsen.

An updated analysisrecentlyshowedsustained efficacy forImfinziplus chemotherapyafter a median followup of more than two years(OSHR: 0.75; 95%CI0.62-0.91; nominal p=0.0032), with median OS of 12.9 months versus 10.5 months for chemotherapy alone.The safety and tolerability forImfinziplus chemotherapy were consistent with the known safety profile of these medicines. No patients tested positive fortreatment-emergent anti-drug antibodies to Imfinzi.

The CASPIAN trial used a fixed dose ofImfinzi(1500mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks until disease progression.

Imfinzi in combination with etoposide and either carboplatin or cisplatin is also approved in the US, Japan and several other countries for the treatment of ES-SCLC in the 1st-line setting and is currently under regulatory review in other countries.

As part of a broad development programme, Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the Phase III ADRIATIC trial.

Small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one fifth of all cancer deaths.4 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC.5 About two thirds of SCLC patients are diagnosed with ES-SCLC, in which the cancer has spread widely through the lung or to other parts of the body.6 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.6

CASPIAN

CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial was conducted in more than 200 centres across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms. In June 2019, AstraZeneca announced the CASPIAN trial had met one primary endpoint of demonstrating OS forImfinziplus chemotherapy at a planned interim analysis. In March 2020, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.

Imfinzi

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on results from Phase III PACIFIC trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumours.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

An extensive Immuno-Oncology (IO) development programme focuses on lung cancer patients without a targetable genetic mutation, which represent up to three quarters of all patients with lung cancer.7 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON and PEARL) and for patients in earlier stages of disease, including potentially-curative settings (Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy.Imfinziis also in development in the Phase II trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline, includingEnhertu.

AstraZenecas approach to IO

IO is a therapeutic approach designed to stimulate the bodys immune system to attack tumours. The Companys IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZenecas Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients lives and the Companys future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visitastrazeneca.comand follow the Company on Twitter@AstraZeneca.

References

1. National Cancer Institute. NCI Dictionary Small Cell Lung Cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed July 2020.

2. Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? Journal of Oncology Practice, 2018:14;369-370.

3. Paz-Ares L, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. The Lancet. 2019;394(10212):1929-1939.

4. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed July 2020.

5. LUNGevity Foundation. Types of Lung Cancer. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed July 2020.

6. Cancer.Net. Lung Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/33776/view-all. Accessed July 2020.

7. Pakkala, S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3(15):e120858.

SOURCE: AstraZeneca

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Imfinzi approved in the EU for the treatment of extensive-stage small cell lung cancer | Antibodies | News Channels - PipelineReview.com

Sept. 1, 2020 12:05 UTC

~25-35 % survival over 5 years from diagnosis in vaccinated GBM patients vs a historical rate of ~ 5%

ROCKVILLE, Md. & SAN DIEGO--(BUSINESS WIRE)-- Immunomic TherapeuticsInc., (ITI), a privately-held clinical-stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, announced today that results from multiple ATTAC clinical studies of dendritic cell vaccines have been published online by American Association for Cancer Research (AACR) in an article titled, Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.

ITI is developing several dendritic cell vaccines for the treatment of cancer, including ITI-1000 for glioblastoma (GBM), with leaders in cancer immunotherapy for brain tumors, John Sampson, M.D., Ph.D. from Duke University and Duane Mitchell, M.D., Ph.D. from the University of Florida. ITIs dendritic cell vaccine is designed to target the pp65 viral antigen of Cytomegalovirus (CMV) that is expressed in GBM, but not in normal brain cells.

In the ATTAC studies, the GBM patients white blood cells are removed, matured into dendritic cells (DCs), and modified to generate a vaccine to the pp65 viral protein when fused to the LAMP1 protein for antigen presentation. This DC vaccine is then returned to the patient. As observed in the ATTAC studies, ITI believes this approach may harness the bodys immune system to recognize, attack and destroy tumor cells that express CMV in GBM and potentially other cancers. The published results from the three original ATTAC clinical studies are summarized below:

Three separate clinical trials conducted by Drs. Mitchell and Sampson utilized Cytomegalovirus specific dendritic cell vaccines in patients with newly diagnosed glioblastoma.

The three small studies (total n = 26; NCT#s 00639639, 2366728) revealed that overall 5-year survival increased from a historical low of 5% to 25%. However, in two of the studies, vaccination site pre-conditioning with either Td or GM-CSF:

This data is preliminary, and additional studies are needed.

These study results not only advance our understanding of a virus role in cancer, but they also signal tremendous hope to patients and their families suffering from this devastating disease, Sampson said. I look forward to continued evaluation of ITIs dendritic cell vaccines, including ITI-1000, in the ongoing, randomized, placebo-controlled ATTAC-II study.

GBM is the most aggressive form of brain cancer, often resulting in a patients death within one to two years from diagnosis. Historically, it is a very difficult disease to treat and current treatment options offer limited benefit to extend survival, added Mitchell. The results demonstrated with CMV-specific dendritic vaccines in the ATTAC studies are very encouraging, particularly in the observation of a significant fraction of long-term survivors and favorable safety profile of the vaccine platform. We remain steadfast in our pursuit to identify effective treatments for patients with GBM and look forward to the continued evaluation of ITIs vaccines in addressing this clear and pressing unmet medical need.

The AACR article can be found here.

About Glioblastoma (GBM)

According to the American Association of Neurological Surgeons, GBM is an aggressive brain cancer that often results in death within 15 months of diagnosis. GBM develops from glial cells (astrocytes and oligodendrocytes), grows rapidly, and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents about 15% of all primary brain tumors and approximately 10,000 cases of GBM are diagnosed each year in the U.S.

About ITI-1000 and the Phase 2 (ATTAC-II) Study

ITI-1000 is an investigational dendritic cell vaccine therapy currently in a Phase 2 clinical trial (ATTAC-II) for the treatment of GBM. ITI-1000 was developed using Immunomics proprietary investigational lysosomal targeting technology, UNITE, in the context of cell therapy. In May 2017, Immunomic exclusively licensed a patent portfolio from Annias Immunotherapeutics for use in combination with UNITE and ITI-1000, allowing Immunomic to combine UNITE with a patented and proprietary CMV immunotherapy platform. The ATTAC-II study (NCT02465268) is a Phase II randomized, placebo-controlled clinical trial enrolling patients with newly diagnosed GBM that will explore whether dendritic cell (DC) vaccines, including ITI-1000, targeting the CMV antigen pp65 improves survival. This study is enrolling up to 120 subjects at 3 clinical sites in the United States. For more information on the ATTAC-II study, please visit http://www.clinicaltrials.gov.

About UNITE

ITIs investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein 1, an endogenous protein in humans, for immune processing. In this way, ITIs vaccines (DNA or RNA) have the potential to utilize the bodys natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach puts UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in a Phase II clinical trial as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

About Immunomic Therapeutics, Inc.

Immunomic Therapeutics, Inc. (ITI) is a privately-held, clinical stage biotechnology company pioneering the development of vaccines through its proprietary technology platform, UNiversal Intracellular Targeted Expression (UNITE), which is designed to utilize the bodys natural biochemistry to develop vaccines that generate broad immune responses. UNITE has a robust history of applications in various therapeutic areas, including infectious diseases, oncology, allergy and autoimmune diseases. ITI is primarily focused on applying the UNITE platform to oncology, where it could potentially have broad applications, including viral antigens, cancer antigens, neoantigens and antigen-derived antibodies as biologics. The Company has built a large pipeline from UNITE with six oncology programs and two allergy programs. ITI has entered into a significant allergy partnership with Astellas Pharma and has formed several academic collaborations with leading Immuno-oncology researchers at Fred Hutchinson Cancer Research Institute, Johns Hopkins University of Medicine, University of Florida, and Duke University. ITI maintains its headquarters in Rockville, Maryland. For more information, please visit http://www.immunomix.com.

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Immunomic Therapeutics Announces Publication of Results from 3 ATTAC Studies of CMV-Specific Dendritic Cell Vaccines for the Treatment of GBM -...

Despite many treatments for inflammatory bowel disease (IBD), a number of patients fail to respond long-term. In a new study, a team of researchers led by scientists at the University of California, San Diego (UCSD), School of Medicine, reported that the lasting nature of IBD may be due to a type of long-lived immune cell that can provoke persistent, damaging inflammation in the intestinal tract.

The research team integrated single-cell RNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls.They sought to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC).

The work is published in the article, Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses, inScience Immunology.

We took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells, said Gene W. Yeo, PhD, professor of cellular and molecular medicine at UCSD School of Medicine, and analyzed thousands of individual cells, which is quite exciting.

It has long been believed that immune system dysfunction, in concert with genetic susceptibility and changes in the gut microbiome, plays a significant role in IBD. However, the types of immune cells involved and their specific contributions to IBD have remained unclear. CD8+ T cells are one component of the immune system that identify and kill cells infected by microbial pathogens.

When an infection has been conquered, the immune system leaves behind long-lasting cells called memory T cells, which reside in tissues or circulate through the body remembering past pathogens, ever ready to sound the alarm should specific invaders reappear.

The resulting single-cell sequencing resource revealed heterogeneity among tissue-resident memory T cells (TRM) in UC, with several subtypes of CD8+ tissue-resident memory T (TRM) cells, a specific class of memory cell that resides in organs once formed.

One of these TRMcell subtypes was distinguished by high levels of the transcription factor Eomesodermin and programmed to produce large amounts of cytokines and other molecules to kill newly detected infected cells. The downside is that excessive, persistently high levels of some cytokines can cause inflammation and tissue damage.

We found that this inflammatory TRMcell subtype seemed to be enriched in the intestinal tissues of patients with ulcerative colitis, a form of IBD that affects the colon, said John T. Chang, MD, professor of medicine at UCSD School of Medicine. Long-lived memory cells are a goal of vaccines, but this finding suggests that these same cells, coveted in the fight against infectious diseases, may actually be harmful in the context of IBD.

The researchers also found evidence that this inflammatory TRMcell subtype might not remain confined to intestinal tissue, but may also escape into the bloodstream.

This may explain why IBD can affect not just the intestines, but many other parts of the body as well, said Boland, a gastroenterologist at UCSD Health and assistant adjunct professor of medicine.

Taken together, the authors wrote that these results provide a detailed atlas of transcriptional changes occurring in adaptive immune cells in the context of UC and suggest a role for CD8+ TRM cells in IBD. They asserted that identifying this TRM population, and other disease-associated T and B cell subsets, provides a platform for future functional studies addressing how these subsets conspire to trigger chronic mucosal injury in UC.

Chang said the findings may help to explain why IBD is chronic and life-long, and point to the possibility of a remedy in the future: Targeting this inflammatory TRMcell subtype for elimination, thus ending the cycle of inflammation and tissue damage.

The researchers noted that much more work is needed to gain a deeper understanding of the role of tissue-resident memory T cells in IBD and to determine whether they can be targeted therapeutically.

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IBD Inflammation Linked to Long-Lived Immune Cell - Clinical OMICs News

As medical researchers rush to find a vaccine for Covid-19, the stories of earlier medical breakthroughs offer hope, but also reasons to be cautious about the timescale and effectiveness of any discovery.

In The Vaccine Race, Meredith Waldman describes how in the early 1960s scientists at Philadelphias Wistar Institute began working on a vaccine for rubella (German measles) using a controversial new method: germ-free cells from tissue extracted from an aborted foetus from a woman in Sweden. The Wistar cells were to revolutionise vaccine making, but ethical and political roadblocks meant it was 10 years before the institute was granted a patent, and it was not until 1978 that the Federal Drug Administration granted the pharmaceutical company Merck a licence for the vaccine in the US.

Waldmans book has uncanny parallels with the Rebecca Skloots The Immortal Life of Henrietta Lacks. This bestseller shows how the cervical cancer cells harvested in 1951 from an African American woman, Henrietta Lacks, gave rise to the immortal HeLa cell line. Lackss cells, which were taken without her consent, were instrumental in the development of the human papilloma virus (HPV) vaccine and other important therapies, but to this day Lackss family has not received compensation for her contribution to medical research.

Few breakthroughs can be more important than James Watson, Francis Crick and Maurice Wilkinss Nobel prize-winning discovery of the helical structure of DNA a story told in Watsons hugely popular but partial 1968 memoir The Double Helix. As Brenda Maddox explains in Rosalind Franklin: The Dark Lady of DNA, it was Franklins photograph of the molecule, shown to Watson without Franklins knowledge, that confirmed their intuition. Feminist scholars have sought to portray Franklin, who died in 1958 and who was overlooked for the 1962 Nobel prize, as the Sylvia Plath of molecular biology. However, in her remarkable book based on Franklins personal correspondence, Maddox shows Franklin maintained a close friendship with Watson and Crick until her death.

You may not have heard of monoclonal antibodies, or Mabs. But as Lara Marks explains in The Lock and Key of Medicine, these microscopic protein molecules, discovered in the mid-70s in the same Cambridge laboratory where Watson and Crick worked on DNA, quietly affect almost every aspect of our lives and have at least as great a claim to have revolutionised medicine. The applications of Mabs include organ transplantation, recombinant interferon and insulin, and personalised drug therapies such as Herceptin.

Generations of medical students have been inspired to go into research by Sinclair Lewiss 1925 novel Arrowsmith. Lewis teamed up with the science writer Paul de Kruif to write this tale of a small-town boy, Martin Arrowsmith, who rises to the pinnacle of medical science by discovering a phage therapy for plague. The prose is a little overwrought for modern tastes, but the novel was a runaway bestseller and is still worth reading for its account of the commercial pressures and professional rivalries endemic to science. Like his hero, who after treating plague on a remote Caribbean island turns down an offer to head up his old laboratory in New York, Lewis was averse to professional plaudits. In 1926 he declined the Pulitzer prize for fiction, claiming he had no desire to tickle the prejudices of a haphazard committee. A Nobel prize could be at stake for the discovery of a vaccine for Covid-19, but present-day medical researchers might wish to bear Lewiss scepticism in mind.

The Pandemic Century by Mark Honigsbaum is published by WH Allen (20). To order a copy go to guardianbookshop.com. Delivery charges may apply.

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The best books about medical breakthroughs - The Guardian

Some taste cells are multitaskers that can detect bitter, sweet, umami and sour stimuli, a new study finds.

The research challenges conventional notions of how taste works. In the past, it was thought that taste cells were highly selective, capable of discerning only one or two types of the five basic stimuli only sweet, for instance, or only salty and sour. Though many cells are indeed specialists, the discovery of a subset of cells that can respond to up to four different tastes suggests that taste science is more complex than previously thought.

The study was published on Aug. 13 in the journal PLOS Genetics. The research was done on mice, which have a very similar taste system to humans, says Kathryn Medler, associate professor of biological sciences, College of Arts and Sciences, who led the study with first author Debarghya Dutta Banik.

This changes the way weve been thinking about how taste cells function and how taste information is collected in a taste bud and sent back to the brain, Medler says. Our data fills in a lot of holes. Other research has suggested that taste cells can be broadly responsive, but we were able to isolate individual taste cells and describe how they work. I cannot definitively state that humans have these broadly responsively taste cells, but based on the high degree of similarity between the mouse and human taste systems, I predict that these cells are very likely present in humans.

It is currently believed that taste cells are very specific about what stimuli they detect. The surprising thing with this new cell population is that individual cells can detect bitter, sweet, umami as well as sour stimuli, says Dutta Banik, a postdoctoral fellow in anatomy, cell biology and physiology in the Indiana University School of Medicine. Dutta Banik did the research while pursuing his doctorate at UB. It was surprising to know that individual taste cells can respond to so many taste qualities.

Taste cells are critical to survival: They help us decide whether a food is a good source of nutrients or a potential poison.

Beyond identifying the multitasking taste cells, the new study describes some of their traits. Scientists showed that the cells detect sour stimuli using one signaling pathway, and sweet, bitter and umami stimuli using a different pathway.

Experiments also showed that when broadly responsive taste cells are silenced, mice have trouble tasting sweet, bitter and umami stimuli. This was the case even when the more selective taste cells those that specialize in detecting individual stimuli remained active, says study co-author Ann-Marie Torregrossa, assistant professor of psychology, College of Arts and Sciences, and associate director of UBs Center for Ingestive Behavior Research.

We did a series of taste tests, says Torregrossa, who led the behavioral aspects of the study. When the animals were missing the function of either the broadly responsive cells or of the traditional taste cells, they responded to sweet, bitter and umami solutions as if they were water. This is very exciting because it suggests they needed both cells to taste the solution normally. When we did the same taste tests with animals that had both cells, they as you would expect licked the sweet solution avidly and avoided the bitter.

This shows that both of these cell populations are important for sending the taste information to the brain, Dutta Banik says.

The groundbreaking findings highlight how much scientists still have to learn about taste, including how taste buds work and send information to the brain.

Compared to other sensory systems, we know surprisingly little about how taste is coded and processed, Torregrossa says. This study identifies a new population of cells that are contributing to normal taste function, which could be a large piece in the puzzle.

The studys co-authors also included Eric D. Benfey, Amy R. Nelson, Zachary C. Ahart, Barrett T. Kemp and Bailey R. Kemp in the Department of Biological Sciences, and Laura E. Martin, Kristen E. Kay and Gregory C. Loney in the Department of Psychology. The research received support from the UB North Campus Imaging Facility, which is funded by the National Science Foundation.

More here:
New type of taste cell discovered in mice - University at Buffalo Reporter

Live Cell Imaging Market: Overview

Live cell imaging is the use of time lapse microscopy to study the living cells. The scientists use it to get a better understanding of the biological functions with the help of cellular dynamics. The live cell imaging technique is becoming increasingly popular in the healthcare industry.

The live cell imaging market can be categorized by products, by technologies, by end users and by regions. By product types, the live cell imaging market can be segmented into instruments, consumables and softwares. The instruments segment can be further sub-divided into standalone systems, cell analyzers, microscopes and image capturing devices. By technologies, the market can be segmented into fluorescence recovery after photobleaching (FRAP), fluorescence resonance energy transfer (FRET), high content screening (HCS), fluorescence in situ hybridization (FISH), ratiometric imaging, total iternal reflection fluorescence microscopy (TRIF), and multiphoton excitation microscopy (MPE) among others. Furthermore, the market can be segmented by applications into pharmaceutical industry, contract research organization, government and academic organization and diagnostic laboratories.

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Live Cell Imaging Market: Trends and Opportunities

The rising concern of cancer is one of the major factors behind the growth of increasing demand of this technology. Furthermore, the government is actively taking initiatives to fund cell based research. Moreover the live cell imaging has a wide area of application and it can used to understand dynamic processes and cellular structures. In addition, it can also be used to study cellular integrity, protein trafficking, enzyme activity, localization of molecules, exocytosis and endocytosis among others. Furthermore, the process can also be applied to monitor the molecules in live animals. Moreover, the pharmaceutical companies are increasingly using live cell imaging in research and development in order to develop new medicines. In addition, the live cell imaging is also used for high content screening.

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However, the cost of implementing live cell imaging is very high is acting as a restraint for the market. Moreover, the technology requires highly skilled professional in order to study and understand the cell functions. The lack of availability of skilled professional is also expected to restrain the growth of live cell imaging market. However, with increasing investments in training and development programs this factor is expected to have low impact in the long run. In addition, the live cell imaging technique is gradually being applied by pharmaceutical companies to develop personalized medicine. This demand is expected to grow in future.

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Live Cell Imaging Market: Geographical and Competitive Dynamics

By geography, the market can be divided into North America, Europe, Asia Pacific and Rest of the world. North America and Europe are the early adapters of technology. Furthermore, government initiatives are being taken in this region for research and development using live cell imaging. U.S. is the largest market for live cell imaging in North America. However, Asia Pacific region is expected to witness robust growth due to presence of developing nations such as India and China.The key players in the live cell imaging market are Sigma-Aldrich Corporation, Nikon Corporation, GE Healthcare, Carl Zeiss AG, Danaher Corporation, Olympus Corporation and Thermo Fisher Scientific, Inc., Molecular Devices, LLC, Becton, Dickinson and Company and Perkinelmer, Inc. among others.

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Live Cell Imaging Market: Rising concern of cancer is one of the major factors behind the market growth - BioSpace

DetailsCategory: DNA RNA and CellsPublished on Sunday, 30 August 2020 13:01Hits: 458

Long-term results from Phase 2/3 Starbeam study (ALD-102/LTF-304) suggest durability of response post eli-cel with all 20 patients who were free of major functional disabilities (MFDs) at two years (out of 23 evaluable patients) remaining MFD-free through last available follow-up, including all 10 patients who reached at least Year 5 follow-up visit

31 out of 32 patients in ALD-102 had stable Neurologic Function Scores following treatment with eli-cel, including 24 patients with a score of zero as of the last available visit

In clinical studies of eli-cel to date, there have been no reports of graft failure, graft rejection, graft-versus-host disease (GVHD), replication competent lentivirus, or insertional oncogenesis

Company on track to submit Marketing Authorization Application in EU by year-end 2020, and Biologics License Application in U.S. in mid-2021

CAMBRIDGE, MA, USA I August 29, 2020 I bluebird bio, Inc. (Nasdaq: BLUE) announced updated results from the clinical development program for its investigational elivaldogene autotemcel (eli-cel, Lenti-D) gene therapy in patients with cerebral adrenoleukodystrophy (CALD), including long-term results from the Phase 2/3 Starbeam study (ALD-102/LTF-304) and data from the Phase 3 ALD-104 study. These data were presented today at the 46th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2020), taking place virtually from August 29 - September 1, 2020.

CALD is a fatal neurodegenerative disease primarily affecting young boys. Currently, the only treatment available is allogeneic hematopoietic stem cell transplantation (allo-HSCT), which comes with associated, significant risks, including transplant-related mortality, graft failure or rejection, and graft-versus-host disease (GVHD), said David Davidson, M.D., chief medical officer, bluebird bio. Eighty-seven percent of patients in our Phase 2/3 Starbeam study of eli-cel are alive and free of major functional disabilities (MFDs) at 24 months or more of follow-up. Importantly, there were no reports of graft failure, graft rejection, or GVHD. It is gratifying to see the consistent outcomes with eli-cel and the durability of the treatment effect demonstrated in the children participating in our long-term follow-up study including 10 boys who have now reached at least their Year 5 follow-up visit.

Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that is estimated to affect one in 21,000 male newborns worldwide. ALD is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently cause toxic accumulation of very long-chain fatty acids (VLCFAs) primarily in the adrenal cortex and white matter of the brain and spinal cord.

Approximately 40% of boys with adrenoleukodystrophy will develop CALD, the most severe form of ALD. CALD is a progressive neurodegenerative disease that involves breakdown of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Symptoms of CALD usually occur in early childhood and progress rapidly, if untreated, leading to severe loss of neurologic function, and eventual death, in most patients. CALD is associated with six MFDs, which severely compromise a patients ability to function independently: loss of communication, cortical blindness, need for tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement. Nearly half of boys with CALD who do not receive treatment will die within five years of symptom onset.

Patients with CALD experience a rapid decrease in neurologic function after the initial onset of clinical symptoms, so early diagnosis and treatment is critical in order to stop the disease progression and preserve their neurological function. In the Phase 2/3 Starbeam study, 31 of 32 patients had a stable neurologic function score, suggesting that disease progression had stabilized and minimal neurological function was lost, following eli-cel infusion, said Dr. Jrn-Sven Khl, Department of Pediatric Oncology, Hematology and Hemostaseology, Center for Women's and Children's Medicine, University Hospital Leipzig. These results presented at EBMT 2020 are very encouraging and suggest treatment with eli-cel may prevent neurological decline in boys with CALD.

Eli-cel is a one-time investigational gene therapy designed to address the underlying genetic cause of CALD by adding functional copies of the ABCD1 gene into a patients own hematopoietic (blood) stem cells (HSCs) that have been transduced ex vivo with the Lenti-D lentiviral vector (LVV). The addition of a functional gene allows patients to produce the ALDP, which is thought to break down the toxic accumulation of VLCFAs in the brain. There is no need for donor HSCs from another person, as is required for allo-HSCT.

Starbeam Study (ALD-102)/Long-Term Follow-Up Study (LTF-304)

The ALD-102 study has completed enrollment. All reported data below are as of January 2020 and reflect a total population of 32 patients with a median follow-up time of 30.0 months (9.1 70.7 months).

Of the 32 patients who have received eli-cel as of January 2020, 20 have completed ALD-102 and enrolled in a long-term follow-up study (LTF-304). Nine additional patients continue to be followed in ALD-102 and have not reached 24 months post-treatment. As previously reported, two patients withdrew from the study at investigator discretion, and one experienced rapid disease progression early on-study resulting in MFDs and death. To date, 104.3 patient-years of follow-up have been reported for ALD-102 and LTF-304.

The primary efficacy endpoint in the study is the proportion of patients who are alive and free of MFDs at Month 24. Of those patients who have or would have reached Month 24, 87% have met the primary endpoint and continue to be alive and MFD-free at more than two years of follow-up (N=20/23). Fourteen patients have at least four years of follow-up, including 10 patients who have reached at least their Year 5 follow-up visit. The nine patients from ALD-102 that have not reached Month 24 have shown no evidence of MFDs.

Data on several secondary and exploratory efficacy outcomes are reported, including changes in neurologic function score (NFS), a 25-point score used to evaluate the severity of gross neurologic dysfunction across 15 symptoms in six categories; resolution of gadolinium enhancement (GdE), an indicator of active inflammation in the brain; and change in Loes score, an MRI measurement of white matter changes in CALD. Of the 32 patients treated, 31 had stable NFS following treatment with eli-cel, defined as NFS <4, without a change of >3 from baseline, and 24 patients maintained an NFS of 0. An NFS of 0 indicates that there are no concerns with the neurologic functions that are assessed on the 25-point scale. Loes scores generally stabilized within 12-24 months and GdE was no longer seen in most patients following eli-cel treatment.

The primary safety endpoint is the proportion of patients who experience acute (Grade 2) or chronic GvHD by Month 24. GvHD is a condition that may occur after an allo-HSCT, where the donated cells view the recipients body as foreign and attack the body. No events of acute or chronic GvHD have been reported post-eli-cel treatment. There have been no reports of graft failure or graft rejection.

In addition, there have been no cases of replication competent lentivirus or insertional oncogenesis to date. Integration site analysis (ISA) was conducted to determine the pattern of integration post-eli-cel infusion and assess whether dominant or expanding clones were present. In one patient, now enrolled in LTF-304 for long-term follow up, a case of benign clonal expansion was observed with three separate integrations in the DNA of the cell at ACER3, RFX3, and MECOM. As of the patients Month 62 visit in March 2020, the patient remained clinically stable. Bone marrow analyses showed no dysplasia (abnormal cell growth) or molecular abnormalities.

The treatment regimen, comprising mobilization/apheresis, conditioning, and eli-cel infusion, had a safety and tolerability profile primarily reflective of the known effects of mobilization/apheresis and conditioning. In ALD-102, as previously reported, three adverse events (AE) were considered possibly related to drug product and include one serious AE (SAE), BK viral cystitis (N=1, SAE, Grade 3), and two non-serious AEs, vomiting (N=2, Grade 1). All three AEs resolved using standard measures.

ALD-104 Study

bluebird bio is currently enrolling patients for ALD-104, a Phase 3 study designed to assess the efficacy and safety of eli-cel in patients with CALD after myeloablative conditioning using busulfan and fludarabine, a different chemotherapy conditioning regimen than what is used in ALD-102 (busulfan and cyclophosphamide). The primary efficacy endpoint is the proportion of patients who are alive and free of MFDs at Month 24, and the primary safety endpoint is the proportion of patients with neutrophil engraftment after eli-cel infusion. All reported data below are as of February 2020.

In ALD-104, the 13 patients currently on study have a median of 6.1 months of follow-up to date (min-max: 2.2 10.3 months). All 13 patients achieved neutrophil engraftment and 12/13 evaluable patients had platelet engraftment (platelet engraftment pending in one patient as of data cut date). Due to the limited duration of follow-up, only safety data are being presented.

No events of acute or chronic GvHD have been reported and there have been no reports of graft failure, graft rejection, cases of insertional oncogenesis, or replication competent lentivirus.

The treatment regimen, comprising mobilization/apheresis, conditioning, and eli-cel infusion had a safety and tolerability profile primarily reflective of the known effects of mobilization/apheresis and conditioning. In ALD-104, two AEs of pancytopenia were considered possibly related to eli-cel. These two ongoing AEs were deemed as suspected unexpected serious adverse reactions (SUSARs) by the principal investigator and were diagnosed approximately two months post-eli-cel infusion in two patients (one Grade 2 and one Grade 3). An additional AE was ongoing as of February 2020, a Grade 3 SAE of transverse myelitis that was diagnosed in the presence of viral infection (adenovirus and rhinovirus/enterovirus positivity) approximately six months after eli-cel infusion and deemed unrelated to eli-cel.

eli-cel Presentation at EBMT

Lenti-D hematopoietic stem cell gene therapy stabilizes neurologic function in boys with cerebral adrenoleukodystrophy

Presenting Author: Dr. Jrn-Sven Khl, Department of Pediatric Oncology, Hematology and Hemostaseology, Center for Women's and Children's Medicine, University Hospital Leipzig Poster Session & Number: Gene Therapy; ePoster O077

Presentations will be available for virtual viewing throughout the duration of the live meeting on the EBMT 2020 website and content will be accessible online following the close of the meeting until November 1, 2020.

About elivaldogene autotemcel (eli-cel, formerly Lenti-D)

In July 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) granted an accelerated assessment to eli-cel gene therapy for cerebral adrenoleukodystrophy (CALD). bluebird bio is currently on track to submit the Marketing Authorization Application (MAA) in the EU for eli-cel for CALD by year-end 2020, and the Biologics License Application (BLA) in the U.S. in mid-2021.

bluebird bio is currently enrolling patients for a Phase 3 study (ALD-104) designed to assess the efficacy and safety of eli-cel after myeloablative conditioning using busulfan and fludarabine in patients with CALD. Contact This email address is being protected from spambots. You need JavaScript enabled to view it. for more information and a list of study sites.

Additionally, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-304) for patients who have been treated with eli-cel for CALD and completed two years of follow-up in bluebird bio-sponsored studies.

The Phase 2/3 Starbeam study (ALD-102) has completed enrollment.

For more information about bluebird bio-sponsored studies visit: http://www.bluebirdbio.com/our-science/clinical-trialsor clinicaltrials.gov.

The European Medicines Agency (EMA) accepted eli-cel gene therapy for the treatment of CALD into its Priorities Medicines scheme (PRIME) in July 2018, and previously granted Orphan Medicinal Product designation to eli-cel.

The U.S. Food and Drug Administration (FDA) granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation for the treatment of CALD.

Eli-cel is not approved for any indication in any geography.

About CALD Early Diagnosis

Early diagnosis of CALD is important, as the outcome of available treatment varies with the clinical stage of the disease. Newborn screening for ALD is a critical enabler of early diagnosis and thus of successful treatment of ALD. Once a patient has been diagnosed with ALD, regular MRI scans are critical to detect white matter changes indicative of progression to CALD.

In the U.S., newborn screening for ALD was added to the Recommended Universal Screening Panel in February 2016 and is currently active in 17 states, accounting for > 58 percent of U.S. newborns. Outside the U.S., the Minister of Health in the Netherlands has approved the addition of ALD to their newborn screening program. Even though ALD newborn screening has not been implemented in most EU countries, efforts to begin pilot programs are slowly progressing.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

SOURCE: bluebird bio

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bluebird bio Presents New Results from Clinical Development Program of elivaldogene autotemcel (eli-cel, Lenti-D) Gene Therapy for Cerebral...

Miao Mo,1 Shiyu Tong,1 Tao Li,2 Xiongbing Zu,1 Xiheng Hu1

1Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, Peoples Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, Peoples Republic of China

Correspondence: Xiheng HuDepartment of Urology, Xiangya Hospital, Central South University, Changsha 410008, Peoples Republic of ChinaEmail huxhxycsu@yeah.net

Background: Chemokine (C-X-C motif) ligands (CXCLs) are important regulators of tumor progression in many cancers and could serve as potential cancer biomarkers. However, the expression patterns as well as functions of CXCLs remain unclear in penile cancer (PC). The aim of this study was to evaluate the usefulness of serum CXCL13 as a potential cancer biomarker for PC.Patients and Methods: This retrospective study enrolled 76 patients diagnosed with PC between 2016 and 2018. Serum CXCL13 level was detected by enzyme-linked immunosorbent assay. Univariable and multivariable Cox regression analyses were conducted to identify the prognostic factors that influence disease-free survival. Human penile cancer cell lines Penl1, Penl2, 149RCa and LM156 were used as in vitro models. The expression of CXCL13 protein in PC cell lines was analyzed by Western blotting.Results: Our initial analysis on GSE57955 dataset identified CXCL13 as a top CXCL gene enriched in PC. Higher preoperative serum CXCL13 level was detected in PC cohorts than in healthy male controls (P< 0.001). The area under the curve was 0.911 with the sensitivity of 84.2% and specificity of 87.0% to distinguish PC. Preoperative serum CXCL13 level was associated with pathological grade (P=0.048), T stage (P=0.009), nodal status (P< 0.001) and pelvic lymph node metastasis (P=0.005) in PC. Serum CXCL13 level could serve as an independent prognostic factor for disease-free survival with a HR of 3.818 (95%CI: 1.126 12.946). Furthermore, autocrine expression of CXCL13 was detected in PC tissues and cell lines. Knockdown of CXCL13 expression suppressed malignant phenotypes (cell proliferation, clonogenesis, apoptosis escape, migration and invasion), attenuated STAT3 and ERK1/2 signaling and reduced MMP2/9 secretion in PC cell lines.Conclusion: Serum CXCL13 could serve as a novel diagnostic and prognostic biomarker for PC. CXCL13 signaling might activate oncogenic signaling pathways to promote malignant progression of PC.

Keywords: penile cancer, CXCL13, cancer biomarker, tumor progression

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Serum CXCL13 Level is Associated with Tumor Progression and Unfavorabl | OTT - Dove Medical Press

Despite significant progress in treating cancer in recent years, the need for further improvements has persisted particularly for some of the most challenging forms of the disease, such as lung cancer. Lung cancer is one of the most common cancers, and is the leading cause of cancer death in both men and women.

The majority of lung cancer cases are non-small cell lung cancer (NSCLC), a complex disease that can affect each patient differently. Most cases of NSCLC are not diagnosed until the disease is advanced meaning it has metastasized or spread which can make it more challenging to treat.

The impact of lung cancer, and advanced NSCLC in particular, continues to be felt across our communities, explained Andrea Ferris, president and chairman of LUNGevity Foundation. While every persons experience with the disease is unique, many patients hope they can retain a sense of normalcy in their lives and are seeking more treatment options that offer a chance at a longer life.

Research Driving New Progress for Certain Patients

Researchers have accelerated their pursuit of new and differentiated approaches that address this critical unmet need, focusing on options that may offer patients a chance at a longer life. One area of research that has shown potential is combining treatments, such as immunotherapies, for certain patients with previously untreated advanced disease.

Hossein Borghaei, D.O., chief of thoracic medical oncology at Fox Chase Cancer Center in Philadelphia explains, Progress in treating advanced lung cancer has led to more options for patients with newly diagnosed advanced NSCLC. Some of the most recent developments in the field of immunotherapy are particularly exciting.

One example is the U.S. Food and Drug Administrations approval of the first and only dual immunotherapy approach for newly diagnosed patients. Opdivo (nivolumab) is a prescription medicine used in combination with Yervoy (ipilimumab) for adults with advanced stage NSCLC that has spread to other parts of your body (metastatic) and tests positive for PD-L1 and do not have an abnormal EGFR or ALK gene.

Opdivo can cause problems that can sometimes become serious or life threatening and can lead to death. Serious side effects may include lung problems (pneumonitis); intestinal problems (colitis) that can lead to tears or holes in your intestine; liver problems (hepatitis); hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas); kidney problems, including nephritis and kidney failure; skin problems; inflammation of the brain (encephalitis); problems in other organs; and severe infusion reactions; and complications of stem-cell transplant that uses donor stem cells (allogeneic). Additional serious side effects of Yervoy alone include: nerve problems that can lead to paralysis; eye problems; and complications of stem-cell transplant that uses donor stem cells (allogeneic). Please see Important Facts about side effects for Opdivo and Yervoy below.

Opdivo and Yervoy work with your immune system to help fight cancer in two ways. Yervoy stimulates the kind of cells that help fight cancer, while Opdivo may help these cells to find and fight the cancer cells again. While doing so, Opdivo and Yervoy can also affect healthy cells. These problems can sometimes become serious or life threatening and can lead to death. These problems may happen anytime during treatment or even after treatment has ended. Some of these problems may happen more often when Opdivo is used in combination with Yervoy.

Clinical Trial Findings: A Chance to Live Longer

Opdivo + Yervoy was studied in a clinical trial and compared to platinum-based chemotherapy among certain patients with previously untreated, advanced NSCLC that tested positive for PD-L1.

In the trial, 396 patients received Opdivo + Yervoy and 397 patients received platinum-based chemotherapy. Patients who were treated with Opdivo + Yervoy lived longer than those treated with platinum-based chemotherapy:

In the trial, 396 patients received Opdivo + Yervoy and 397 patients received platinum-based chemotherapy. Patients who were treated with Opdivo + Yervoy lived longer than those treated with platinum-based chemotherapy:

An additional analysis showed:

The data supporting this dual immunotherapy approach are encouraging, particularly as one third of the patients who responded to treatment with Opdivo + Yervoy were still alive at three years, said Dr. Borghaei. Further, Opdivo + Yervoy offers a non-chemotherapy option, which can be important to some patients.

The most common side effects of Opdivo, when used in combination with Yervoy, include: feeling tired; diarrhea; rash; itching; nausea; pain in muscles, bones, and joints; fever; cough; decreased appetite; vomiting; stomach-area (abdominal) pain; shortness of breath; upper respiratory tract infection; headache; low thyroid hormone levels (hypothyroidism); decreased weight; and dizziness. Please see Important Facts about side effects for Opdivo and Yervoy below.

Evolving Outlooks and Adapting Support for Patients

Facing a lung cancer diagnosis and beginning treatment can be life-altering in many ways and todays unique environment as a result of the coronavirus has brought about additional considerations for patients, caregivers and the broader healthcare community, with telemedicine and other forms of remote support playing an increasingly vital role.

Patients should know there are resources available and ways to stay connected, even during times when maintaining physical distance from others is important, said Ferris. We have transformed many of our patient support and education offerings into virtual formats, which we are updating frequently to provide the most recent information and reach and connect as many people as possible.

Dr. Borghaei also urges patients to reach out to their doctor or care team to learn about and take advantage of available remote support offerings. Advances in cancer research are still happening every day, with Opdivo + Yervoy being one example. Its as important as ever that people diagnosed with lung cancer speak with their doctor to fully understand their treatment options. While how we deliver care might look different now in some ways, our commitment to helping patients live longer hasnt changed.

To learn more about Opdivo + Yervoy, please visit http://www.Opdivo.com.

INDICATION

OPDIVO (nivolumab) is a prescription medicine used in combination with YERVOY (ipilimumab) as a first treatment for adults with a type of advanced stage lung cancer (called non-small cell lung cancer) when your lung cancer has spread to other parts of your body (metastatic) and your tumors are positive for PD-L1, but do not have an abnormal EGFR or ALK gene.

It is not known if OPDIVO is safe and effective in children younger than 18 years of age.

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.

ImportantSafetyInformationforOPDIVO(nivolumab) + YERVOY (ipilimumab)

OPDIVO is a medicine that may treat certain cancers by working with your immune system. OPDIVO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended. Some of these problems may happen more often when OPDIVO is used in combination with YERVOY.

YERVOY can cause serious side effects in many parts of your body which can lead to death. These problems may happen anytime during treatment with YERVOY or after you have completed treatment.

Serious side effects may include:Lung problems (pneumonitis). Symptoms of pneumonitis may include: new or worsening cough; chest pain; and shortness of breath. Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include: diarrhea (loose stools) or more bowel movements than usual; blood in your stools or dark, tarry, sticky stools; and severe stomach area (abdomen) pain or tenderness. Liver problems (hepatitis). Signs and symptoms of hepatitis may include: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); drowsiness; dark urine (tea colored); bleeding or bruising more easily than normal; feeling less hungry than usual; and decreased energy.Hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas). Signs and symptoms that your hormone glands are not working properly may include: headaches that will not go away or unusual headaches; extreme tiredness; weight gain or weight loss; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness; hair loss; feeling cold; constipation; voice gets deeper; and excessive thirst or lots of urine. Kidney problems, including nephritis and kidney failure.Signs of kidney problems may include: decrease in the amount of urine; blood in your urine; swelling in your ankles; and loss of appetite. Skin problems.Signs of these problems may include: rash; itching; skin blistering; and ulcers in the mouth or other mucous membranes. Inflammation of the brain (encephalitis). Signs and symptoms of encephalitis may include: headache; fever; tiredness or weakness; confusion; memory problems; sleepiness; seeing or hearing things that are not really there (hallucinations); seizures; and stiff neck. Problems in other organs. Signs of these problems may include: changes in eyesight; severe or persistent muscle or joint pains; severe muscle weakness; and chest pain.

Additional serious side effects observed during a separate study of YERVOY alone include: Nerve problems that can lead to paralysis. Symptoms of nerve problems may include: unusual weakness of legs, arms, or face; and numbness or tingling in hands or feet. Eye problems.Symptoms may include: blurry vision, double vision, or other vision problems; and eye pain or redness.

Get medical help immediatelyif you develop any of these symptoms or they get worse. It may keep these problems from becoming more serious. Your healthcare team will check you for side effects during treatment and may treat you with corticosteroid or hormone replacement medicines. If you have a serious side effect, your healthcare team may also need to delay or completely stop your treatment.

OPDIVO and OPDIVO + YERVOY can cause serious side effects, including: Severe infusion reactions. Tell your doctor or nurse right away if you get these symptoms during an infusion: chills or shaking; itching or rash; flushing; difficulty breathing; dizziness; fever; and feeling like passing out.Graft-versus-host disease, a complication that can happen after receiving a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic), may be severe, and can lead to death, if you receive YERVOY either before or after transplant. Your healthcare provider will monitor you for the following signs and symptoms: skin rash, liver inflammation, stomach-area (abdominal) pain, and diarrhea.

Pregnancy and Nursing: Tell your healthcare provider if you are pregnant or plan to become pregnant. OPDIVO and YERVOY can harm your unborn baby. If you are a female who is able to become pregnant, your healthcare provider should do a pregnancy test before you start receiving OPDIVO. Females who are able to become pregnant should use an effective method of birth control duringtreatmentand for at least 5 months after the last dose. Talk to your healthcare provider about birth control methods that you can use during this time. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment. You or your healthcare provider should contact Bristol Myers Squibb at 1-800-721-5072 as soon as you become aware of the pregnancy. Pregnancy Safety Surveillance Study: Females who become pregnant during treatment with YERVOY are encouraged to enroll in a Pregnancy Safety Surveillance Study. The purpose of this study is to collect information about the health of you and your baby. You or your healthcare provider can enroll in the Pregnancy Safety Surveillance Study by calling 1-844-593-7869. Before receiving treatment, tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if either treatment passes into your breast milk. Do not breastfeed during treatment and for 5 months after the last dose.

Tell your healthcare provider about: Your health problems or concerns if you: have immune system problems such as autoimmune disease, Crohns disease, ulcerative colitis, lupus, or sarcoidosis; have had an organ transplant; have lung or breathing problems; have liver problems; or have any other medical conditions. All the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of OPDIVO, when used in combination with YERVOY, include: feeling tired; diarrhea; rash; itching; nausea; pain in muscles, bones, and joints; fever; cough; decreased appetite; vomiting; stomach-area (abdominal) pain; shortness of breath; upper respiratory tract infection;headache; low thyroid hormone levels (hypothyroidism); decreased weight; and dizziness.

These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatchor call 1-800-FDA-1088.

Please see U.S. Full Prescribing Information and Medication Guide forOPDIVO and YERVOY.

2020 Bristol-Myers Squibb Company.

OPDIVO and YERVOY are registered trademarks of Bristol-Myers Squibb Company.

7356US2001251-01 08/20

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