Stem Cell Clinic

Team finds way to enhance stem cell therapy for CNS injuries – BioPharma-Reporter.com

The scientists, Christopher Rathnam and colleagues, say they have designed a way of controlling the formation of 3D spheroids made from stem cells, while enhancing the spheroids ability to differentiate into functional neurons.

The technology led to an increase in stem cell survival and differentiation two challenges with existing stem cell therapy systems in a mouse model of spinal cord injury, noted the team in a paper published inScience Advances

We believe that our technology platform is an ideal candidate for improving many other types of cell therapies that require high cell survival and effective control of cell fate, making it useful not only for treating [spinal cord injuries] but also for various other diseases and disorders, said the authors.

Although stem cell therapy holds enormous potential for treating debilitating injuries and diseases of the CNS, the team outlined how low survival and inefficient differentiation have restricted its clinical applications.

Recently, 3D cell culture methods, such as stem cellbased spheroids and organoids, have demonstrated advantages by incorporating tissue-mimetic 3D cell-cell interactions, said the experts.

However, a lack of drug and nutrient diffusion, insufficient cell-matrix interactions, and tedious fabrication procedures have compromised their therapeutic effects in vivo, they added.

To address these issues, the Rathnam led team developed a method in which biodegradable manganese dioxide nanosheets guide the rapid assembly of neural stem cells, derived from human induced pluripotent stem cells (iPSCs), into 3D spheroids.

The technique also enables controlled drug release inside the core of the spheroids, which could help to improve cell survival and differentiation, they said.

To evaluate the efficacy of the structures, which they termed synthetic matrix-assisted and rapidly templated (SMART) spheroids, the researchers implanted them at injury sites in a mouse model of spinal cord injury.

As controls, they injected cell suspensions and conventional neurospheres, formed without the use of their novel nanosheets, at the spinal cord injury sites, with the same total number of cells per animal and at the same concentrations.

They found significantly higher cell survival and improved neuronal differentiation efficiency for the SMART neurospheres compared with the controls both 7 days and 1 month after injection.

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Team finds way to enhance stem cell therapy for CNS injuries - BioPharma-Reporter.com

Bacterial Infections Linked with Unapproved Stem Cell Treatments – Contagionlive.com

Unproven products marketed as stem cell therapies could be risky, according to a new study from the Centers for Disease Control and Prevention, which analyzed bacterial infections from unapproved products derived from umbilical cord blood.

The case series study, published in JAMA Network Open, examined 20 bacterial infections in eight states. It involved reviewing medical records, sterility testing of products and whole-genome sequences of patient and product isolates for participants who developed bacterial infections after receiving stem cell treatments between August 2017 and September 2018.

The findings of this investigation show that stem cell therapies that are not FDA-approved or that are not used for the approved medical conditions can pose serious health risks to patients with no benefit, Kiran Mayi Perkins, MD, lead investigator with the CDCs Outbreak and Response Team, told Contagion. Currently, the only stem cell products derived from umbilical cord blood that are FDA-approved for use in the United States are approved for use in patients with disorders that affect the production of blood, but they are not approved for other uses. However, these products are often illegally marketed by clinics as being safe and effective for treating a wide range of diseases or conditions. Therefore, patients should be aware of the unproven benefits and the potential risks to their health when using unapproved and unproven stem cell products for conditions that they have not been shown to effectively treat.

All but one of the patients in the study required hospitalization after receiving stem cell treatment for conditions including osteoarthritis, rheumatoid arthritis and injury. The CDC performed sterility testing on vials of product and compared bacterial isolates with those from the patients.

We were surprised by the magnitude of bacterial contamination found in the vials that we tested; over half of the vials of the stem cell product that we tested were contaminated with bacteria, and many of these vials had very high bacterial counts, Perkins said.

Unapproved stem cell products have been marketed for conditions such as joint diseases, sports injuries and chronic pain and have become more prevalent as people seek products to prevent and treat COVID-19, the study noted. However, these uses are not approved by the US Food and Drug Administration (FDA).

ReGen Series products processed by Genetech and distributed by Liveyon were recalled after bacterial infections were reported in Texas and Florida in 2018, and a national investigation was launched. Information was gathered about patients, product administration, infection control practices and product manufacturing and distribution.

The bottom line is that many stem cell clinics are offering unproven products that have the potential to be dangerous, Perkins said. There is good research that is being done on stem cell therapies, but there are also a lot of clinics that are selling stem cells for unproven uses. To date, the only stem cell treatments approved by the FDA are products made from a donors umbilical cord blood that are used to treat certain cancers and disorders of the blood and immune system. If the cells are being used to treat other conditions such as pain, orthopedic conditions, autism, anti-aging, or COVID-19, they are not approved and may not be safe. We urge all patients and health care practitioners considering stem cell therapies to ensure that the stem cell product is being used for the approved indication or under an Investigational New Drug Application (IND) and is on FDAs list of approved products.

The states in which confirmed bacterial infections were identified as of March 2021 are Texas, Florida, California, Arizona, Kansas, Maine, Colorado and Massachusetts.

The treatments were injected into the patients knees, shoulders, spine or digits or administered through intravenous infusion or as a nasal spray. Infections included 10 at the injection site, five bloodstream infections and five with both injection site and bloodstream infections. Most common bacteria were Escherichia coli and Enterobacter cloacae.

CDC will continue to investigate any reports that it receives that are concerning for infectious risks to patients associated with the receipt of stem cell products and will report these to FDA, the agency that has regulatory oversight for these types of therapies, Perkins said.

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Bacterial Infections Linked with Unapproved Stem Cell Treatments - Contagionlive.com

Stem Cells Used to Treat Avascular Necrosis of the Femoral Head – Yale School of Medicine

Collapsed femoral heads caused by osteonecrosisotherwise known as avascular necrosis unfortunately represent the root cause for approximately 10% of all hip replacements nationwide. Daniel Wiznia, MD, is utilizing a stem cell treatment at Yale School of Medicine and integrating new techniques along with 3D imaging technology as part of a joint-preservation procedure.

Occurring in more than 20,000 Americans each year, osteonecrosis of the femoral head is commonly diagnosed in patients in their 30s and 40s. The disease is caused by injury of the blood supply to the head of the femur, which is the ball portion of the hips ball and socket joint.

If unaddressed, this disease may ultimately lead to the collapse of the femoral head, requiring the patient to undergo a hip replacement. For patients in this age group, a total hip replacement is not ideal as it likely will wear out and the patient will require more surgery.

The goal for each case is clear: prevent the femoral head from collapsing and the need for a hip replacement. As part of a surgical procedure, Wiznia harvests bone marrow from the patients pelvis. The individuals own stem cells are then isolated from the marrow, concentrated, and injected into lesions within the avascular portion of the femura treatment that is only taking place at some of the nations largest medical centers.

The key in these instances is to discover the avascular necrosis before the head collapses, Wiznia said. Because the vascular injury is usually a painless event, patients are generally unaware of the specific point in time when the vascular injury occurred, which is why cases are rarely discovered in time. However, we do know that 80% of patients who have avascular necrosis on one side of the hip have it on the opposite side. We usually are able to catch that second asymptomatic side in those situations and conduct the core decompression with stem cell treatment before it collapses.

According to Wiznia, this treatment reduces the risk of the head of the femur from collapsing, and the stem cell therapy has shown promising results. Soon after the procedure, many patients with avascular necrosis experience rejuvenated blood supply to the area and the bone is repopulated with new cells. This can additionally alleviate the short-term need for a hip replacement.

This novel stem cell therapy has demonstrated improved pain and function, and the stem cells decrease the risk of the femoral head from collapsing, Wiznia said. This translates into fewer young patients requiring hip replacements, and subsequent surgeries in their later years.

As an engineer himself, Wiznia works closely with the Yale School of Engineering & Applied Sciences and the Integrated 3D Surgical Team to better tailor this treatment to each specific patient.

One of the challenges of orthopaedic surgery in the human body is that surgeons are operating in a three-dimensional space and are often reliant on two-dimensional imagery such as X-rays, Wiznia added. Through the use of computer modeling, we are able to customize those images and create models that are specific to each patient, which, in turn, enhances outcomes and overall post-operative success rates.

Enhanced models and 3D imaging enable surgeons like Wiznia to better locate and target both the lesions and necrotized bone in these instances. Effectively doing so regenerates the femoral head and stimulates new osteoblast growth, which will heal the region, maintain the integrity of the joint, and decrease the chance of femoral head collapse and need for a hip replacement.

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Stem Cells Used to Treat Avascular Necrosis of the Femoral Head - Yale School of Medicine

Stem cell therapy can help combat common symptoms of aging – The Mountaineer

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Vitti Labs Announces FDA Approval of IND Application for Phase II Clinical Trial of Combination Mesenchymal Stem Cell and Exosome Treatment of Novel…

LIBERTY, Mo., Oct. 26, 2021 /PRNewswire/ -- Vitti Labs (www.vittilabs.com), an AATB Accredited Tissue Bank focused on Life Science Research, Development and Manufacturing, announced today that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application to conduct Phase II Clinical Trials using a combination of Umbilical Cord Mesenchymal Stem Cell and Umbilical Cord Mesenchymal Stem Cell Exosomes for the treatment of Acute Respiratory Distress Syndrome (ARDS) associated with the Novel Corona Virus (COVID-19). This marks the very first time the FDA has approved an IND that uses both of these components together and so first of its kind therapy.

This therapy is designed to suppress the pro-inflammatory processes in the pulmonary system that occurs in COVID patients, while simultaneously alleviating pulmonary distress, such as acute lung injury and inflammation as seen in ARDS (Acute Respiratory Distress Syndrome). In addition to its anti-inflammatory and anti-fibrotic properties, the combination therapy aims to reduce oxidative stress. This Phase II study will evaluate the utility of intravenous umbilical cord mesenchymal stem cells and exosomes in mitigating the pulmonary consequences of COVID-19. As this treatment has already shown tremendous promise in the treatment for ARDS associated with COVID-19, the completion of this Phase II Clinical Trial is expected to conclude in Q1 of 2022.

Philipp Vitti, Chief Scientist of Vitti Labs, stated, "We are very excited to be the first FDA Approved IND to have Umbilical Cord Mesenchymal Stem Cells and their Exosomes being utilized together as a multi-dose combination therapy for IV use. The preliminary trials have been overwhelmingly successful. Mesenchymal Stem Cells and their exosomes have unique therapeutic benefits, and together they create advanced therapeutic properties. This application approval is a great advancement in the ongoing progress to utilize Umbilical Cord Mesenchymal Stem Cells and Exosomes for different disease models, and Vitti Labs is excited and proud to contribute their resources to finding effective treatment options for the worldwide pandemic."

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About Vitti Labs

Vitti Labs is a cGMP certified, AATB accredited Tissue bank in Liberty, Missouri. They harvest biomaterials from the umbilical cord and placenta to utilize their properties to activate and support the repair of the body. Vitti Labs has a commercial division which focuses on human cellular tissue products. Vitti Labs' research and development division focuses on understanding various disease models and utilizing umbilical cord and placental derived Mesenchymal Stem Cells and Exosomes for therapies of those diseases.

For any media requests/inquiries: Miriam McKinney, 816-200-7959, 322286@email4pr.com

http://www.vittilabs.com

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Vitti Labs Announces FDA Approval of IND Application for Phase II Clinical Trial of Combination Mesenchymal Stem Cell and Exosome Treatment of Novel...

Biohaven Enrolls Phase 1a/1b Clinical Trial of BHV-1100, Lead Asset from its ARM (Antibody Recruiting Molecule) Platform, in Combination with NK Cell…

-- Biohaven initiates a clinical trial of the novel antibody recruiting molecule BHV-1100 to assess safety, tolerability, and exploratory clinical activity in Multiple Myeloma

Published: Oct. 27, 2021 at 7:30 AM EDT|Updated: 18 hours ago

NEW HAVEN, Conn., Oct. 27, 2021 /PRNewswire/ --Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN), announced the enrollment of the first patient in a Phase 1a/1b trial in Multiple Myeloma using the ARM, BHV-1100, in combination with autologous cytokine induced memory-like (CIML) natural killer (NK) cells and immunoglobulin (Ig) to target and kill multiple myeloma cells expressing the cell surface protein CD38 (Figure 1). BHV-1100 is the lead clinical asset from Biohaven's ARM Platform, developed from a strategic alliance with PeptiDream Inc. This clinical trial will assess the safety and tolerability, as well as exploratory efficacy endpoints, in newly diagnosed multiple myeloma patients who have tested positive for minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT).

NK cells are part of the innate immune system, which is designed to recognize and destroy "non-self" or diseased cells in the body. However, tumor cells can evade detection by immune effector cells, allowing the tumor to advance. BHV-1100 targets a cell-surface protein, CD38, that is heavily overexpressed on multiple myeloma and binds to it, recruiting primed autologous cytokine induced memory-like (CIML) natural killer (NK) cells to destroy the tumor.

Charlie Conway, Ph.D., Chief Scientific Officer at Biohaven commented, "While many recent advances have been made to benefit multiple myeloma patients, most patients will unfortunately still relapse. We are excited to investigate BHV-1100 for its ability to recruit autologous CIML NK cells to the site of the tumor. Based on preclinical data from Biohaven Labs, we anticipate that our CD38 targeting ARM-enabled NK cells will kill CD38-positive multiple myeloma cells, and recruit other immune effector cells to assist in reducing the tumor burden."

Biohaven has initiated enrollment in the clinical trial and plans to enroll 25 patients for this single-center, open-label study (ClinicalTrials.gov Identifier: NCT04634435; https://clinicaltrials.gov/ct2/show/NCT04634435). The study will enroll newly diagnosed multiple myeloma patients who have minimal residual disease (MRD+) in first remission prior to an autologous stem cell transplant (ASCT).

David Spiegel M.D., PhD, inventor of the ARM technology and Professor of Chemistry and Pharmacology at Yale University, commented, "This is an important milestone in the development of the ARM therapeutic platform taking a novel technology from 'benchtop to bedside'. It also highlights Biohaven's commitment to benefit patients in need."

About ARMs: Antibody Recruiting Molecules

ARMs,antibody recruiting molecules, are engineered with modular components that are readily interchangeable, giving the platform tremendous flexibility and rapid development timelines. ARM compounds are being developed at Biohaven Labs to redirect a patient's own antibodies for therapeutic effect with multiple benefits over traditional monoclonal antibody therapies, including the potential for oral dosing. For BHV

1100, the ARM platform is being used to provide antigen targeting to NK cell-based therapies without genetic engineering. This NK cell targeting approach is also being investigated with allogeneic, or 'off-the-shelf', immune cell-based therapies.

About Multiple Myeloma Multiple myeloma is a type of blood cancer of the plasma cell that develops in the bone marrow, the soft tissue inside our bones. Healthy plasma cells produce antibodies, which are critical for the immune system's ability to recognize disease-causing entities, such as bacteria, viruses and tumor cells. In multiple myeloma, however, genetic abnormalities in a single plasma cell cause it to divide uncontrollably. This leads to the over-production of a single (monoclonal) antibody protein, referred to as an "M protein". Also, these cancerous cells divide to the point of crowding out normal, healthy cells that reside in the bone marrow. Many patients are diagnosed due to symptoms such as bone pain or fractures, kidney failure (thirst, dehydration, confusion), nerve pain, fever, and weakness. The American Cancer Society estimates that approximately 34,920 new cases will be diagnosed, and 12,410 deaths will occur in 2021 from multiple myeloma.

About BiohavenBiohaven is a commercial-stage biopharmaceutical company with a portfolio of innovative, best-in-class therapies to improve the lives of patients with debilitating neurological and neuropsychiatric diseases, including rare disorders and areas of unmet need. Biohaven's neuro-innovation portfolio includes FDA-approved NURTEC ODT (rimegepant) for the acute and preventive treatment of migraine and a broad pipeline of late-stage product candidates across three distinct mechanistic platforms: CGRP receptor antagonism for the acute and preventive treatment of migraine; glutamate modulation for obsessive-compulsive disorder, Alzheimer's disease, and spinocerebellar ataxia; and MPO inhibition for amyotrophic lateral sclerosis. More information about Biohaven is available atwww.biohavenpharma.com.

About PeptiDream PeptiDream Inc. is a public(Tokyo Stock Exchange 1st Section 4587) biopharmaceutical company founded in 2006 employing their proprietary Peptide Discovery Platform System (PDPS), a state-of-the-art highly versatile discovery platform which enables the production of highly diverse (trillions) non-standard peptide libraries with high efficiency, for the identification of highly potent and selective hit candidates, which then can be developed into peptide-based, small molecule-based, or peptide-drug-conjugate-based therapeutics. PeptiDream aspires to be a world leader in drug discovery and development to address unmet medical needs and improve the quality of life of patients worldwide. Further information regarding PeptiDream can be found at: http://www.peptidream.com.

Forward-looking Statement This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve substantial risks and uncertainties, including statements that are based on the current expectations and assumptions of Biohaven's management about BHV-1100 as a treatment for multiple myeloma. Forward-looking statements include those related to: Biohaven's ability to effectively develop and commercialize BHV-1100, delays or problems in the supply or manufacture of BHV-1100, complying with applicableU.S.regulatory requirements, the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials, the timing of planned interactions and filings with the FDA, the timing and outcome of expected regulatory filings, the potential commercialization of Biohaven's product candidates, the potential for Biohaven's product candidates to be firstin class or best in class therapies and the effectiveness and safety of Biohaven's product candidates. Various important factors could cause actual results or events to differ materially from those that may be expressed or implied by our forward-looking statements. Additional important factors to be considered in connection with forward-looking statements are described in the "Risk Factors" section of Biohaven's Annual Report on Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission onMarch 1, 2021, and Biohaven's subsequent filings with the Securities and Exchange Commission. The forward-looking statements are made as of this date and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

NURTEC and NURTEC ODT are registered trademarks of Biohaven Pharmaceutical Ireland DAC. Neuroinnovation is a trademark of Biohaven Pharmaceutical Holding Company Ltd.

ARM is a trademark of Kleo Pharmaceuticals, Inc.

Biohaven Contact Dr. Vlad Coric Chief Executive Officer Vlad.Coric@biohavenpharma.com

Media Contact Mike Beyer Sam Brown Inc. mikebeyer@sambrown.com 312-961-2502

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The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

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Biohaven Enrolls Phase 1a/1b Clinical Trial of BHV-1100, Lead Asset from its ARM (Antibody Recruiting Molecule) Platform, in Combination with NK Cell...

The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect – Curetoday.com

Using BK virus (BKV)-specific T cells from healthy donors to treat BKV-associated hemorrhagic cystitis, a painful side effect associated with immunosuppression from stem cell transplants, may relieve the complication faster in patients with lymphoma or leukemia, according to trial results.

What was very important was that within a week of giving the cells, the majority of patients symptoms improved, Dr. Katy Rezvani, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center in Houston and lead study author, said in an interview with CURE. The effect of the cells is relatively rapid.

BKV-associated hemorrhagic cystitis occurs more frequently in patients with leukemia or lymphoma who received a treatment of allogeneic stem cell transplantation. As a result, it can lead to patients having blood in their urine and passing clots, which can cause urinary retention (difficulty urinating or completely emptying the bladder) and, in more severe cases, kidney disease.

In patients who receive stem cell transplants, those who have a half match (when patients only have some genetic similarities with the donors immune system) are at an increased risk for BKV-associated hemorrhagic cystitis because they are more immunosuppressed. Approximately 40% of patients who have a half match develop this complication.

In the phase 2 trial, BKV-specific T cells, which recognize and attack BKV, from healthy donors were given once intravenously, with the option to receive additional doses every two weeks if needed. Of the 59 patients enrolled in the trial, 67.7% had complete (all symptoms resolved) or partial (almost all symptoms resolved) responses within 14 days. This increased to 81.6% after 28 days.

Some intolerance was observed in patients who were previously treated with steroids, which can kill T cells. There were no side effects, and there were no reports of new liver or gastrointestinal graft-versus-host disease (GVHD, occurs when the donor's cells attack the patient's cells) associated with the antiviral T cells, aside from a few cases of skin GVHD that quickly resolved with corticosteroids.

This treatment has the potential to stop the vicious cycle that comes with the current standard of care, which consists of hospitalization with continuous bladder irrigation (using a catheter to wash out the bladder) and morphine infusion to help patients tolerate the pain, according to Rezvani.

This outpatient treatment is preventing patients from having to be admitted (to the hospital), which is wonderful because patients come into hospital with one thing, they stay in the hospital for a few weeks, then they develop other complications, Rezvani explained. They start getting other infections, they get pneumonia, they become malnourished, etc.

According to Rezvani, one donor can produce up to 50 doses of T cells, which are frozen until needed. Every time the patient comes (into the hospital), within 24 hours we can treat them, she said.

Of note, the therapy is only available at MD Anderson, so patients with the complication would need to travel to the health center to receive it an option that may not be possible because of physical condition or finances. Im hoping that we will get to a situation where well be able to start a multicenter study at some point, Rezvani said, which would make the care more accessible to patients. In the meantime, I think the greatest limitation really is that patients will have to come to MD Anderson to receive the treatment, and for many patients with the terrible BKV hemorrhagic cystitis, this is not obviously possible.

Until then, Rezvani is focusing on the next generation of the treatment: genetically modifying BKV-specific T cells that are more resistant to steroids, thus broadening the patient spectrum that the treatment could help.

Its important to realize that the use of immunotherapy against viruses and cancers (has) opened up a very exciting new era of treatment for our patients, she concluded. We are learning a lot more from the immune system (and are harnessing) the power of the immune system to fight infections and cancers. ... I think the field is going to continue to grow, and many more such treatments to target both viruses and cancers (are) going to become available.

For more news on cancer updates, research and education, dont forget tosubscribe to CUREs newsletters here.

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The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect - Curetoday.com

Global Cell Therapy Market Research Report 2021: Opportunities with the Approval of Kymriah and Yescarta Across Various Countries -…

DUBLIN--(BUSINESS WIRE)--The "Global Cell Therapy Market Size, Share & Trends Analysis Report by Use-type, by Therapy Type (Autologous, Allogenic), by Region (North America, Europe, Asia Pacific, Latin America, MEA), and Segment Forecasts, 2021-2028" report has been added to ResearchAndMarkets.com's offering.

The global cell therapy market size is expected to reach USD 23.0 billion by 2028 and is expected to expand at a CAGR of 14.5% from 2021 to 2028.

The emergence of new technologies to support the development of advanced cellular therapies has aided in market growth. Companies are leveraging new technologies not only for the expansion of their product portfolio but also for establishing out-licensing or co-development agreements with other entities to support their product development programs.

Cell-based therapies hold great potential for replacing, repairing, restoring, or regenerating damaged tissues, and organs. Researchers are making huge investments in the development of such effective and safe treatments as an alternative to conventional treatment strategies which can be further attributed to the market growth.

Out of all therapeutic areas, oncology has the highest number of ongoing clinical trials. T cells, CD34+ and/or CD133+ stem cells, mesenchymal stem/stromal cells are predominantly employed for clinical investigation.

The majority of biopharmaceutical entities have been affected by the COVID-19 pandemic, while several cellular therapy development companies have witnessed a strongly negative impact, which can be attributed to complications in logistics as well as the manufacturing models employed in this industry. In addition, substantial and stable funding is imperative to ensure successful commercial translation of cell-based therapeutics, a factor that was negatively affected in 2020, further affecting the market growth.

A survey conducted recently among executives of more than 15 European and U.S. cellular therapy companies indicated that disruption caused by the pandemic was significant, which demanded market entities to create strategies to sustain themselves and plan the next wave of innovative therapies.

Key issues faced by companies operating in the market include on-time delivery of therapies to patients at required clinical sites. In addition, the administration of these therapeutics poses several post-pandemic challenges. Hospitals are hesitant in offering services, owing to concerns over transmission of SARS-CoV-2, particularly to vulnerable individuals. Moreover, patients have not been able to visit cellular therapy centers either, owing to the lockdowns and travel bans.

Cell Therapy Market Report Highlights

Market Dynamics

Market driver analysis

Market restraint analysis

Market opportunity analysis

COVID-19 Impact Analysis

Challenges analysis

Opportunities analysis

Challenges in manufacturing cell therapies against COVID-19

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/n1u89x

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Global Cell Therapy Market Research Report 2021: Opportunities with the Approval of Kymriah and Yescarta Across Various Countries -...

Pursuing Optimal Therapy Remains a Challenge in Indolent B-Cell Lymphoma – Targeted Oncology

A significant proportion of patients worldwide live disease-free for a decade or longer following first-line therapy, with various approaches suggesting that there may be pathways to develop approaches for a cure for at least a subset of patients

Follicular lymphoma (FL) and other forms of indolent non-Hodgkin lymphoma (iNHL) are commonly considered incurable diseases with continual risk of relapse over time, shorter durations of response with each subsequent line of therapy, and a risk of transformation to a more aggressive B-cell lymphoma. Although these lymphomas are characterized as indolent, one of the most common causes of death for these patients is lymphoma.1 On the other hand, a significant proportion of patients worldwide live disease-free for a decade or longer following first-line therapy, with various approaches suggesting that there may be pathways to develop approaches for a cure for at least a subset of patients.1-5 In the Indolent B-Cell Lymphoma session during the Society of Hematologic Oncology 2021 Annual Meeting, 4 presentations were explored: Molecular Pathogenesis of Follicular Lymphoma and Its Relevance to Clinical Practice, Sequencing Therapy in Follicular Lymphoma, Novel Therapies in Indolent Lymphoma, and CAR T-Cell Therapy in Indolent Lymphoma in lectures by world-class experts Jessica Okosun, MA, MB BChir, MRCP, FRCPath, PhD, Peter Martin, MD, Loretta Nastoupil, MD, and Caron Jacobson, MD, MMSc.

Next-generation sequencing studies, led by Michael R. Green, PhD, Dr Okosun, and others, have described the panoply of genomic events involved in FL and have aided in identifying candidate genetic drivers.6-9 This work clarified the diverse genomic landscape and the temporal clonal dynamics of FL. Common genomic events that occur with t(14;18) include high frequencies of mutations affecting epigenetic regulation, disruptions in pathways such as those involved in immune recognition (eg, TNFRSF14), NF-KB (eg, CARD11), and JAK/STAT signaling (eg, STAT6).9,10 Next-generation sequencing also has been used to examine factors associated with progression of FL, transformation of iNHL to more aggressive lymphomas, and spatial heterogeneity in FL. Recent studies have explored the subclonal diversity and spatial heterogeneity observed among patients with FL that have potential clinical implications for the development of prognostic and predictive biomarkers and targeted treatment strategies. For instance, exome sequencing of FL tumors and paired germline have identified nonsynonymous somatic variants corresponding to missense (81%), indels (10%), nonsense (7%), and splice site (2%) changes.6 This work revealed spatially discordant mutations in genes such as EZH2 and EP300. One attractive treatment paradigm emerging from this work involves specifically targeting highly recurrent and truncal gene mutations that have roles in FL pathogenesis. Other studies did not identify a single compelling genetic event responsible for transformation, but instead suggest that the acquisition of certain genetic alterations may result in aggressive transformation.7,9,11 Exploration of the FL genomics in this session can clarify stratified treatment approaches targeting specific early genetic lesions identified in FL and may eventually provide strategies to eradicate these cell populations and provide pathways to cure FL.

In the past decade, many new agents have been introduced for the management of FL, and therapeutic strategies have evolved over time. Recently, my co-chair in this session, Nathan Fowler, MD, and I reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory FL.12 However, since that review other agents have received FDA approval for patients with relapsed FL. There is considerable variation in response rates for recently approved therapies ranging from objective response rates of 40% to 60% for PI3K inhibitors, 35% to 65% for EZH2 inhibitors, and greater than 70% for autologous stem cell transplantation, and CD19-directed chimeric antigen receptor (CAR) T-cell therapy.13-18 Recently approved therapies in relapsed FL have commonly been based on response rate and duration of response (DOR) demonstrated in phase 2 studies. However, despite numerous trials performed in the field, there is no single standard of care for patients with iNHL who are undergoing second-line treatment or beyond.

As a result of the patterns of relapse and transformation associated with iNHL, the clinical treatment of patients with FL and other iNHLs often requires multiple lines of therapy using various regimens with different mechanisms of action.19-22 The clinical benefits and adverse effects associated with the treatments available at relapse vary and are influenced by patient and disease characteristics at the time of progression, the duration of the interval from last treatment, and the toxicity and responses associated with the treatments previously administered. This results in a marked heterogeneity of clinical situations encountered during the treatment of these patients. Some patients with iNHL will remain well treated using available treatments, whereas others will develop disease refractory to conventional approaches and become candidates for novel treatments and clinical trials. Additional real-world data regarding patient characteristics at relapse, patterns of care, expectations of response rates and duration, and survival outcomes are lacking in the setting of relapsed and refractory iNHL. To help inform treatment decisions by health care providers treating patients with iNHL in this complex and evolving treatment landscape, Dr Martin will describe approaches for sequencing therapies. To optimally individualize treatment strategies for patients with previously untreated and relapsed iNHL, the risks and benefits of the available options should be well known. This lecture will enable providers to effectively discuss the goals of therapy with the patient at each intervention, which is also critical in providing an optimal sequence of therapy.

Although many patients with FL experience long or possibly near-normal life expectancies, there remains persistent variability in patient outcomes.19-22 Patients who relapse within 2 years of first-line chemoimmunotherapy or with histologic transformation are at risk for early mortality and are high-priority candidates for novel treatment strategies evaluated in clinical trials.23-25 Prior studies have demonstrated diminishing DOR by line of therapy.26,27

However, variability of iNHL disease biology, treatment options, and treatment patterns complicate outcome assessments based on line of therapy alone. Several novel and targeted therapies are being developed and evaluated in patients with relapsed iNHL, including cereblon inhibitors, antiCD20-CD3 bispecific antibodies, and additional anti-CD19 CAR T-cell therapies. Dr Nastoupil will provide key insights on the novel therapies available for patients in clinical trials and those that are establishing pathways toward applications in clinical settings.

CAR therapy targeting CD19 is one promising treatment for patients with relapsed or refractory FL and CD19+ iNHLs. Patients who are candidates for CAR T-cell therapy often have symptomatic disease that could be fatal if left untreated. Dr Jacobson will discuss strategies for bridging therapy, which may include chemotherapy, targeted therapy, or radiation therapy; approved and experimental CAR T-cell approaches for FL and iNHLs; and describe traditional and novel adverse events and outcomes from clinical trials involving CAR T-cell therapy.

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Pursuing Optimal Therapy Remains a Challenge in Indolent B-Cell Lymphoma - Targeted Oncology