Category Archives: Stem Cells

Alessandra de Oliveira Pinheiro,1 Valria M Lara,1 Aline F Souza,1 Juliana B Casals,2 Fabiana F Bressan,1 Paulo Fantinato Neto,1 Vanessa C Oliveira,1 Daniele S Martins,1 Carlos E Ambrosio1

1Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of So Paulo, Pirassununga, So Paulo, Brazil; 2Private Veterinary Practice, Pirassununga, So Paulo, Brazil

Correspondence: Carlos E AmbrosioDepartment of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of So Paulo, FZEA- Av. Duque de Caxias Norte, 225, ZMV, Pirassununga 13635-900, So Paulo, BrazilTel +55 19 3565-4113 Email ceambrosio@usp.br

Purpose: Amniotic membrane stem cells have a high capacity of proliferation, cell expansion, and plasticity, as well as immunomodulatory properties that contribute to maternal-fetal tolerance. Owing to the lack of research on human amniotic membrane at different gestational stages, the canine model is considered ideal because of its genetic and physiological similarities. We aimed to characterize the canine amniotic membrane (CAM) cell lineage in different gestational stages and evaluate the expression of immunomodulatory genes.Materials and Methods: Twenty CAMs from early (20 30 days) (n=7), mid- (31 45 days) (n=7), and late gestation (46 63 days) (n=6) stages were studied. The cell features were assessed by cell viability tests, growth curve, colony-forming units, in vitro differentiation, cell labeling for different immunophenotypes, and pluripotent potential markers. The cells were subjected to RT-PCR and qPCR analysis to determine the expression of IDO, HGF, EGF, PGE2, and IL-10 genes.Results: CAM cells exhibited a fibroblastoid morphology and adherence to plastic with an average cell viability of 78.5%. The growth curve indicated a growth peak in the second passage and we obtained an average of 138.2 colonies. Osteogenic, chondrogenic, and adipogenic lineages were confirmed by in vitro differentiation assays. Cellular immunophenotyping experiments confirmed the presence of positive mesenchymal markers (CD90 and CD105) and the low or negative expression of hematopoietic markers (CD45 and CD34). Qualitative analysis of the immunomodulatory functions indicated the expression of the IDO, HGF, EGF5, and PGE2 genes. When stimulated by interferon-gamma, CAM cells exhibited higher IDO levels throughout gestation.Conclusion: The CAMs from different gestational stages presented features consistent with mesenchymal stem cell lineage; better results were observed during the late gestation stage. Therefore, the gestational stage is a key factor that may influence the functionality of therapies when using fetal membrane tissues from different periods of pregnancy.

Keywords: canine stem cells, immunomodulation, fetal annexes

This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License.The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/.The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Characterization and Immunomodulation of Canine Amniotic Membrane Stem | SCCAA - Dove Medical Press

A group of UB researchers have published a paper that clarifies certain cellular mechanisms that could lead to improved outcomes in patients with globoid cell leukodystrophy, commonly known as Krabbe disease.

The paper, titled Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction, was published May 5 in the journal Neuron.

The research was led by Lawrence Wrabetz and M. Laura Feltri. Wrabetz and Feltri head the Hunter James Kelly Research Institute and both are professors in the departments of Biochemistry and Neurology in the Jacobs School of Medicine and Biomedical Sciences at UB.

The institute is named for the son of former Buffalo Bills quarterback Jim Kelly. Hunter Kelly died at age 8 in 2005 from complications of Krabbe disease.

Krabbe disease is a progressive and fatal neurologic disorder that usually affects newborns and causes death before a child reaches the age of 2 or 3.

Traditionally, hematopoietic stem cell transplantation, also known as a bone marrow transplant, has improved the long-term survival and quality of life of patients with Krabbe disease, but it is not a cure.

It has long been assumed that the bone marrow transplant works by a process calledcross-correction, in which an enzyme called GALC is transferred from healthy cells to sick cells.

Using a new Krabbe disease animal model and patient samples, the UB researchers determinedthatin reality cross-correctiondoes not occur. Rather, the bone marrow transplant helps patients through a different mechanism.

The researchers first determined which cells are involved in Krabbe disease and by which mechanism. They discovered that both myelin-forming cells, or Schwann cells, and macrophages require the GALC enzyme, which is missing in Krabbe patients due to genetic mutation.

Schwann cells require GALC to prevent the formation of a toxic lipid called psychosine, which causes myelin destruction and damage to neurons. Macrophages require GALC to aid with the degradation of myelin debris produced by the disease.

The research showed that hematopoietic stem cell transplantation does not work bycross-correction, but by providing healthy macrophages with GALC.

According to Feltri, the data reveal that improvingcross-correctionwould be a way to makebone marrow transplants and other experimental therapies such as gene therapy more effective.

Bone marrow transplantation and other treatments for lysosomal storage disorders, such as enzyme replacement therapy, have historically had encouraging but limited therapeutic benefit, says study first author Nadav I. Weinstock, an MD-PhD student in the Jacobs School. Our work defined the precise cellular and mechanistic benefit of bone marrow transplantation in Krabbe disease, while also shedding light on previously unrecognized limitations of this approach.

Future studies, using genetically engineered bone marrow transplantation or other novelapproaches,may one day build on our findings and eventually bridge the gap for effectively treating patients with lysosomal disease, he continues.

UB investigators included Daesung Shin, research assistant professor at the Hunter James Kelly Research Institute; Nicholas Silvestri, clinical associate professor of neurology, Jacobs School; Narayan Dhimal, PhD student; Chelsey B. Reed, MD-PhD student; and undergraduate student Oliver Sampson.

Also participating in the research were Eric E. Irons, MD-PhD student, and Joseph T.Y. Lau, a distinguished faculty member from the Department of Molecular and Cellular Biology at Roswell Park Comprehensive Cancer Center.

The research was funded by multiple grants from the National Institutes of Health awarded to Weinstock, Shin, Wrabetz and Feltri, and also supported by Hunters Hope.

Excerpt from:
UB investigators uncover cellular mechanism involved in Krabbe disease - UB Now: News and views for UB faculty and staff - University at Buffalo...

PUBLISHED: 13:06 04 May 2020 | UPDATED: 13:18 04 May 2020

Mike Brooke

Sam in the London Clinic... after being matched to save a patient's life in worldwide appeal for stem cell donors. Picture: DKMS charity,

DKMS

A life-saving transplant procedure for Sam Schmidt to donate some of his blood stem cells to help save a patients life has gone well.

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The 24-year-old accounts manager from Limehouse was finally found to be a compatible match for a patient in a worldwide search after registering with a stem cell charity a year ago.

He underwent the procedure at The London Clinic before the weekend to donate stem cells after being successfully matched with a blood cancer patient.

He felt strange being tested due to Covid-19 with everyone having to wear masks and gloves, but felt lucky to have the chance potentially to save someones life and help a family.

Sam registered with the DKMS charity, known as We Delete Blood Cancer, when he moved to Narrow Street in Limehouse last year from west London.

He was inspired after learning about 42-year-old Peter McCleave, a father of two in Cheshire diagnosed with blood cell cancer and given a few years to live.

Peter has launched his own search for donors with his 10,000 people campaign while still waiting for a match. He has attracted potential donors to register with the DKMS Foundation, but so far has found no match to save his own life.

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Sam back home in Limehouse after treatment donating stem cells to help a patient beat blood cancer - East London Advertiser

In its fourth week now, C-CAMPs Covid Innovation Deployment Accelerator (C-CIDA) continues to select top startups across India innovating to fight the coronavirus pandemic. It has managed to select and showcase 30 startups in 30 days that are solving gaps and needs across screening, monitoring, and diagnostics.

Several of these are usingstem cell research. One of them is Bengaluru-based cell therapy startup Eyestem. Founded by Jogin Desai, Rajani Battu, and Dhruv Sareen, the startup aims to develop scalable cell replacement therapies for the world.

Hence, Eyestem believes that the easiest way forward is to repurpose existing drugs and has built an Anti-Covid screening (ACS) platform, which aims to provide the research community with a resource to determine the efficacy of a drug or a vaccine using the closest human host cell population.

Led by Rajarshi Pal, Chief Scientist of Eyestem, the startup had been working on lung cells for a couple of years now, publishing papers on the same. However, in the last three months, it pivoted to build this platform specifically to fight the coronavirus pandemic.

Now, it is ready to partner with other labs and companies to grow SARS-CoV-2 virus in these lung cells and start testing these drugs.

He claims that the startup has already collaborated with two players, and is also expecting to start working with facilities in the US soon.

How has the coronavirus outbreak disrupted your life? And how are you dealing with it? Write to us or send us a video with subject line 'Coronavirus Disruption' to editorial@yourstory.com

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This startup aims to treat coronavirus using stem cell research - YourStory

4 May 2020

A novel stem cell therapy may play a part in improving the survival rate of ventilator-dependent COVID-19 patients.

Twelve COVID-19 patients at Mount Sinai Hospital in New York were treated with a new type of stem cell therapy, resulting ina survival rate of 83 percent, significantly higher than the 12 percent survival rate for similar untreated patients.

Dr Keren Osman who led the team Mount Sinai Hospital, New Yorktold CBS News: 'What we saw in the very first patient was that within four hours of getting the cells, a lot of her parameters started to get better'.

Ryoncil (remestemcel-L) comprises culture-expanded mesenchymal stem cells (MSCs):rare cells that secrete factors that promote tissue repair and modulate an immune response.

The initial trial of Ryoncil with COVID-19 patients included two intravenous infusions of the drug over five days. Ten of the total 12 patients were able to come off ventilators after treatment. All patients had received other experimental therapies before receiving Ryoncil.

Dr Osman said 'we don't know if the ten people taken off ventilators would not have recovered if they had not been given the stem cell treatment and we would never dare to claim that it was related to the cells A randomised controlled trial would be the only way to make a true comparison.'

A300-person randomised, controlled clinical trial is now planned to determine the safety and efficacy of Ryoncil in the treatment of COVID-19 patients suffering from acute respiratory distress syndrome (ARDS), which results when the patient is unable to get enough oxygen and usually requires the use of a ventilator.

The overreaction of the immune system responsible for these effects is often termed a 'cytokine storm', where the systemic response to destroy the virus ends up damaging the infected lung tissue. Cytokines are small proteins released from certain cells in the immune system and play a role in cell signalling. Therapeutic use of Ryoncil is thought to down-regulate pro-inflammatory cytokine production and stimulate increased production of anti-inflammatory cytokines.

Ryoncil is currently under review by the US Food and Drug Administration (FDA) for the treatment of acute graft versus host diseaseand other rare diseases. The drug has been evaluated through several clinical trials, totalling over 1100 patients, including evidence of improved lung function in patients with similar biomarkers to COVID-19 patients with ARDS.

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Investigational new drug may be beneficial in treating severe COVID-19 - BioNews

When the axons that extend from neurons break during a spinal cord injury, the result is often a lifelong loss of motor functioning, because vital connections from the brain to other body parts cannot be restored. Now, researchers from Temple Universitys Lewis Katz School of Medicine say they may have found a way to recover some functions lost to axon breaks.

The researchers discovered that boosting levels of a protein called Lin28 in injured spinal cords of mice prompts the regrowth of axons and repairs communication between the brain and body. Lin28 also helped repair injured optic nerves in the animals, they reported in the journal Molecular Therapy.

The Temple team zeroed in on Lin28 because its a known regulator of stem cells, meaning it controls their ability to differentiate into various cells in the body. The researchers examined the effects of Lin28 on spinal cord and optic nerve injuries using two mouse models: one that was engineered to express extra Lin28 and another that was normal and was given the protein after injury via a viral vector.

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All of the mice experienced axon regeneration, the researchers reported. But they found that the best results occurred in the normal mice that received Lin28 injections post-injury. In fact, in animals with optic nerve injuries, the axons regrew to the point where they filled the entire tract of the nerve.

Lin28 treatment after injury improved coordination and sensation in the mice, the researchers reported.

"We observed a lot of axon regrowth, which could be very significant clinically, since there currently are no regenerative treatments for spinal cord injury or optic nerve injury," said senior author Shuxin Li, M.D., Ph.D., professor of anatomy and cell biology at the Lewis Katz School of Medicine, in a statement.

RELATED: Gene therapy with 'off switch' restores hand movement in rats with spinal cord injury

Lin28 is already a target of interest, though it has garnered the most attention so far in cancer research. Startup Twentyeight-Seven Therapeutics is developing a small molecule that inhibits the protein in the hopes that doing so will boost Let-7, a cancer-suppressing microRNA. The company raised more than $82 million in a series A financing last year.

Several new approaches for repairing spinal cord injuries are under investigation, most notably gene therapy. King's College researchers are working on a gene therapy that repairs axons by prompting the production of the enzyme chondroitinase. A UT Southwestern team is targeting the gene LZK to increase levels of supportive nervous system cells called astrocytes in response to spinal injuries.

The Temple team has a two-pronged approach to further developing their Lin28-directed treatment. They hope to develop a vector that can be safely delivered by injection and that would deliver the therapy directly to damaged neurons. They also plan to study other molecules in the Lin28 signaling pathway.

"Lin28 associates closely with other growth signaling molecules, and we suspect it uses multiple pathways to regulate cell growth," Li said, potentially revealing other therapeutic molecules that could further boost neuron repair.

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Repairing spinal cord injuries with a protein that regulates axon regeneration - FierceBiotech

The Stem Cell Banking Market globally is a standout amongst the most emergent and astoundingly approved sectors. This worldwide market has been developing at a higher pace with the development of imaginative frameworks and a developing end-client tendency.

Given the debilitating impact of COVID-19 (Coronavirus) on the Stem Cell Banking market, companies are vying opportunities to stay afloat in the market landscape. Gain access to our latest research analysis on COVID-19 associated with the Stem Cell Banking market and understand how market players are adopting new strategies to mitigate the impact of the pandemic.

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key players of the global stem cell banking market are NeoStem, Esperite, Smart Cells International, StemCyte, ViaCord, Capricor, CordCare, Cryo Stemcell, Cellartis and Aldagen. The key players from the North America and Europe are contributing major share to the global stem cells banking market.

Overall, the global stem cell banking market has expected to register the significant growth over the forecast period.

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This Stem Cell Banking report begins with a basic overview of the market. The analysis highlights the opportunity and Stem Cell Banking industry trends that are impacted the market that is global. Players around various regions and analysis of each industry dimensions are covered under this report. The analysis also contains a crucial Stem Cell Banking insight regarding the things which are driving and affecting the earnings of the market. The Stem Cell Banking report comprises sections together side landscape which clarifies actions such as venture and acquisitions and mergers.

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Demand for Stem Cell Banking Skyrockets with the Surge in Covid-19 Cases, Supporting Global Revenue - amitnetserver

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced a new development and commercialization agreement with Saladax Biomedical, Inc. (Saladax), a leading diagnostics provider focused on developing blood tests for personalized dosing, to develop and validate a fully automated nanoparticle immunoassay kit designed to simplify and streamline therapeutic drug monitoring (TDM) for patients treated with the conditioning agent busulfan.

At AVROBIO, we push ourselves to be at the forefront of technologies advancing lentiviral gene therapy, and its in this spirit that were funding the development of this kit, said Geoff MacKay, AVROBIOs president and CEO. Our personalized conditioning approach is already delivering results. We believe this new assay kit will, for the first time, provide convenient busulfan TDM close to the patient, potentially improving both the patient experience and long-term outcomes, as well as enabling many more hospitals and clinics to become TDM-capable sites.

AVROBIOs state-of-the-art plato gene therapy platform incorporates TDM protocols designed to optimize busulfan dosing over four days, with the goal of maximizing stem cell engraftment while minimizing side effects. TDM evaluates how quickly a patient metabolizes busulfan a rate that can vary significantly from patient to patient and even from one day to the next for the same patient. Current assays that inform that dose adjustment can take hours to return results and must be processed at specialized laboratories with trained staff that may not be geographically convenient to the gene therapy dosing site.

The technology used to deliver these rapid test results is based on an extensive intellectual property portfolio developed by Saladax in the field of TDM. The new assay kit under development by Saladax, which collects a small blood sample, is able to return results on patient metabolization of busulfan in minutes using hospitals standard analytical devices, greatly expanding access to personalized conditioning with busulfan.

Personalized Gene Therapy to Optimize Durable Protein Expression including in Brain, Muscle and Bone

AVROBIOs investigational gene therapies start with collecting the patients own hematopoietic stem cells. In the companys manufacturing process, a lentiviral vector is used to integrate a therapeutic gene designed to produce functional protein essential to cellular health into the patients chromosomes. Prior to dosing, treating clinicians use busulfan, an extensively validated conditioning agent generally considered to be the gold standard for ex vivo lentiviral gene therapy, to create space in the patients bone marrow. Finally, the patient receives the gene therapy and the therapeutic stem cells are expected to engraft in the bone marrow and produce generations of daughter cells, each containing the therapeutic gene. This approach is designed to drive durable production of the functional protein throughout the patients body, including hard-to-reach tissues such as the brain, muscle and bone. A distinguishing feature of this type of gene therapy with busulfan conditioning is that some of the corrected cells are expected to cross the blood-brain barrier and thereby potentially address central nervous system manifestations.

Earlier this year, AVROBIO reported initial clinical results for the first patient conditioned with busulfan using TDM prior to dosing in AVROBIOs Phase 2 clinical trial of its investigational gene therapy, AVR-RD-01, for Fabry disease. The early data from this patient showed increased endogenous enzyme activity at one month following dosing, as compared to other patients in the trial who received a different conditioning agent. Initial data suggest side effects, including nausea, mucositis, fever, rash and hair loss, which were consistent with those expected based on clinical experience of busulfan, developed eight to 10 days after dosing with busulfan and resolved quickly.

About AVROBIO

Our mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato gene therapy platform, our foundation designed to scale gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits of Saladaxs immunoassay kits, including the ability to improve, simplify and streamline therapeutics drug monitoring for patients treated with the conditioning agent busulfan and enable local commercialization of AVROBIOs proprietary platform worldwide, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety profile of our investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that AVROBIO may not realize the intended benefit of Saladaxs immunoassay kits, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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AVROBIO to Collaborate with Saladax Biomedical on New High-Speed Diagnostic Assay Used with Busulfan Conditioning to Enable Widespread...

The report on the Hematopoietic Stem Cells (HSCs) market provides a birds eye view of the current proceeding within the Hematopoietic Stem Cells (HSCs) market. Further, the report also takes into account the impact of the novel COVID-19 pandemic on the Hematopoietic Stem Cells (HSCs) market and offers a clear assessment of the projected market fluctuations during the forecast period. The different factors that are likely to impact the overall dynamics of the Hematopoietic Stem Cells (HSCs) market over the forecast period (2019-2029) including the current trends, growth opportunities, restraining factors, and more are discussed in detail in the market study.

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The following manufacturers are covered:Kite Pharma Inc.Thermo Fisher ScientificPromoCellCellGenix Technologie Transfer GmbHCesca Therapeutics Inc.R&D SystemsGenlantisLonza Group Ltd.TiGenix N.V.ScienCell Research LaboratoriesChina Cord Blood CorporationVcanbioBoyalifeBeike Biotechnology

Segment by RegionsNorth AmericaEuropeChinaJapanSoutheast AsiaIndia

Segment by TypeLeukocyteLymphocytesRed Blood CellsPlatelets

Segment by ApplicationBlood System DiseasesAutoimmune DiseasesOther

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Assessing the Fallout From the Coronavirus Pandemic Hematopoietic Stem Cells (HSCs) Market Insights on Trends, Application, Types and Users Analysis...

Researchers are learning more about how to diagnose and better treat blastic plasmacytoid dendritic cell neoplasm, a rare cancer that often presents with skin manifestations, according to a review published March 2020 in Current Opinion in Hematology.1

Blastic plasmacytoid dendritic neoplasm patients have suffered historically poor outcomes. Years ago, doctors were limited to treating these patients primarily with intensive chemotherapy regimens used to treat acute myeloid leukemia or acute lymphoblastic leukemia patients.

But in 2018, the U.S. Food and Drug Administration (FDA) approved tagraxofusp-erzs (Elzonris, Stemline).

Tagraxofusp-erz is the first approved drug indicated specifically for blastic plasmacytoid dendritic neoplasm, and its use is recommended in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.Newer targeted agents to treat the hematologic malignancy are in the pipeline.

Notable changes in recent years

The World Health Organization (WHO) named blastic plasmacytoid dendritic cell neoplasm (BPDCN) and classified it under acute myeloid leukemia and related precursor neoplasms in 2008. Some eight years later, WHO established BPDCN as a distinct entity.

Just how many people have BPDCN isnt clear. But it is thought that there are about 0.04 cases of the cancer per 100,000 people. And about three in four patients are older men.

Derived from plasmacytoid dendritic cells, BPDCN generally is an aggressive disease. It presents clinically on the skin in about nine out of every 10 cases. Skin lesions tend to be asymptomatic, often appearing as bruise-like lesions, plaques or nodules, according to the paper.

While a small percentage of patients will present with skin disease only, most show signs of BPDCN in the bone marrow, lymph nodes or visceral organs. Rarely, patients will have no cutaneous evidence and instead present with the leukemic phase of the cancer. About 30% of patients also have central nervous system involvement.

Flow cytometry to determine the immunophenotype is an essential component of diagnosing [blastic plasmacytoid dendritic cell neoplasm], the author wrote.

CD123, an interleukin-3 receptor alpha, is over expressed in nearly all BPDCN cases. These cancer cells also may be positive for CD4, CD56, CD303 or TCL1, according to the paper.

Some authors have found a recurrent MYC gene rearrangement in these patients. That particular genetic aberration is associated with an older age at diagnosis and worse prognosis.

Treatment is evolving

Unfortunately, doctors have to rely largely on retrospective studies looking at BPDCN treatment options.Those studies suggest that BPDCN, generally, responds better to acute lymphoblastic leukemia regimens compared to acute myeloid leukemia treatment options. However, most responses to these regimens are transient, the author reported.

Retrospective studies suggest allogeneic stem cell transplant for eligible patients in their first remission offer the highest overall survival rates, including 3- and 4-year overall survival rates ranging from 74% to 82%.Tagraxofusp-erzs targets CD123. It consists of recombinant human interleukin-3 fused to a truncated diphtheria toxin, according to the paper.

Binding the drug to CD123 on the cell surface leads to cellular internalization of the diphtheria toxin, which ultimately leads to inhibition of protein synthesis and cell death, the author wrote.

In a phase I/II clinical trial of 44 untreated or relapsed/refractory BPDCN patients, 21 of 29 previously untreated patients achieved complete remission and 13 of those went on to have a stem cell transplant. Overall response rate of the 15 patients with relapsed/refractory BPDCN was 67% with tagraxofusp-erzs, with an average overall survival of 8.5 months.

Eighteen of the 44 patients studied developed the most critical treatment-related adverse event, capillary leak syndrome. Two patients died from capillary leak syndrome during the study.Researchers are studying investigational agents aimed at treating BPDCN. These include IMGN632, a humanized antibody-drug conjugate with an anti-CD123 monoclonal antibody conjugated to a DNA-alkylating payload, the author wrote.

Researchers are evaluating the safety and efficacy of treating CD123-positive malignancies including BPDCN with the monoclonal antibody targeting CD123 and CD3 XmAb14045.

Venetoclax, a BCL-2 inhibitor, is yet another agent in the pipeline for BPDCN patients.

as knowledge is gained on the molecular changes that occur in [blastic plasmacytoid dendritic cell neoplasm], this will ideally lead to more targeted and effective therapies in the years to come, the author wrote.

Disclosures:

Kendra Sweet, MD, has received honoraria from Stemline Therapeutics.

References:

1 Sweet K. Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment. Curr Opin Hematol. 2020;27(2):103-107.

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Investigational agents to treat hematologic malignancy in pipeline - Dermatology Times