Category Archives: Stem Cell Medicine

Safety of Stem Cell Therapy for Chronic Knee Pain Confirmed in New Study – SciTechDaily

A study released inSTEM CELLS Translational Medicinehas confirmed the safety of a novel type of cellular therapy for knee pain caused by osteoarthritis. Conducted by a multi-institutional team of researchers in Japan who had developed the new therapy, the study was designed to confirm that their treatment which involves transplanting the patients own mesenchymal stem cells (MSCs) into the affected knee did not cause tumors.

The results showed that five years after transplantation, osteoarthritis-related tears to the knee meniscus had healed and, just as importantly, none of the patients experienced any serious side effects from the treatment. The meniscus is a crescent-shaped cartilage in the knee joint that plays a role in shock absorption. Age-related damage to the meniscus often leads to the progression of osteoarthritis of the knee.

Chronic knee pain is a major issue for the aging, affecting approximately 25 percent of all adults, according to the Centers for Disease Control and Prevention (CDC). Osteoarthritis is the most common cause of this condition in people aged 50 and older. Along with pain, which can be debilitating, knee problems can significantly affect the persons mobility and quality of life.

Knee replacement surgery is the gold standard of treatment, with the majority of people experiencing a dramatic reduction in pain and, thus, improvement in their ability to live a normal life. However, though rare, such surgery does come with risks such as the possibility of infection.

Lead investigator Mitsuru Mizuno, DVM, Ph.D. and corresponding author Ichiro Sekiya, M.D., Ph.D. Credit: AlphaMed Press

Cellular therapies are showing great potential as a less invasive way to treat difficult-to-heal knee injuries. The team behind the current study, which included researchers from Tokyo Medical and Dental University, Kyoto University and Kazusa DNA Research Institute, recently developed a therapy involving the transplantation of MSCs derived from the knees soft tissue (the synovium) into the injured meniscus. MSCs are multipotent adult stem cells present in the umbilical cord, bone marrow, fat, dental and other body tissues. Their ability to secrete biologically active molecules that exert beneficial effects on injured tissues makes them a promising target in regenerative medicine.

But some stem cell treatments have been known to cause tumors, which is why the team wanted to ensure that their therapy was free of any negative side effects. In particular, they wanted to investigate the safety of any MSCs that might show a type of chromosomal disorder called trisomy 7.

Trisomy 7 occurs frequently in patients with severe knee disease such as osteoarthritis. The detection of trisomy 7 in epithelial cells has been associated with tumor formation. However, the safety of these cells after transplantation has not been investigated. Thats what we wanted to learn from this study, said corresponding author Ichiro Sekiya, M.D., Ph. D., director and professor of the Center for Stem Cell and Regenerative Medicine (CSCRM) at Tokyo Medical and Dental University.

Mitsuru Mizuno, DVM, Ph.D., assistant professor with CSCRM, served as the studys lead investigator. He reported on the results. We recruited 10 patients for the study and transplanted their own stem cells into the affected knee joints, then followed up with MRIs over the next five years. The images revealed that tears in the patients knee meniscus were obscured three years after transplantation. We also identified trisomy 7 in three of the patients, yet no serious adverse events including tumor formation were observed in any of them.

Dr. Sekiya added, Keep in mind that these were autologous MSCs used in our study, which means that the transplanted MSCs came from the patients themselves. Any problems that might arise in the case of allogeneic cells, which are donated by someone other than the patient, still need to be determined.

Nevertheless, we believe that these data suggest that MSCs with trisomy 7 are safe for transplantation into human knees and show much promise in treating osteoarthritis.

This study highlights the ability of a patients own stem cells to potentially heal torn cartilage in the knee, said Anthony Atala, M.D., Editor-in-Chief ofSTEM CELLS Translational Medicineand director of the Wake Forest Institute for Regenerative Medicine. These outcomes suggest a potential approach that could change the overall physical health of patients who suffer from osteoarthritis and experience debilitating joint pain. We look forward to the continuation of this research to further document clinical efficacy.

Reference: Transplantation of human autologous synovial mesenchymal stem cells with trisomy 7 into the knee joint and 5 years of follow-up by Mitsuru Mizuno, Kentaro Endo, Hisako Katano, Naoki Amano, Masaki Nomura, Yoshinori Hasegawa, Nobutake Ozeki, Hideyuki Koga, Naoko Takasu, Osamu Ohara, Tomohiro Morio and Ichiro Sekiya, 3 August 2021, STEM CELLS Translational Medicine. DOI: 10.1002/sctm.20-0491

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Safety of Stem Cell Therapy for Chronic Knee Pain Confirmed in New Study - SciTechDaily

Asia-Pacific Cell Therapy Market8 – Opportunities in the Approval of Kymriah and Yescarta – Markets Insider

DUBLIN, Aug. 4, 2021 /PRNewswire/ -- The "Asia Pacific Cell Therapy Market Size, Share & Trends Analysis Report by Use-type (Clinical-use, Research-use), by Therapy Type (Autologous, Allogeneic) and Segment Forecasts, 2021-2028" report has been added to ResearchAndMarkets.com's offering.

The Asia Pacific cell therapy market size is expected to reach USD 2.9 billion by 2028. The market is expected to expand at a CAGR of 14.9% from 2021 to 2028.

Rapid advancements in regenerative medicine are anticipated to provide effective solutions for chronic conditions. A substantial number of companies in the growing markets, such as India and South Korea, are striving to capitalize on the untapped opportunities in the market, thereby driving the market.

The growth is greatly benefitted by the fund and regulatory support from government bodies and regulatory agencies. For instance, in August 2020, the government of South Korea passed an Act on the Safety and Support of Advanced Regenerative Medical Treatment and Medicine to establish a regulatory system for patient safety during quality control and clinical trials and to strengthen the regulatory support for regenerative medicine development.

The implementation of the act is expected to enhance clinical studies and approvals of regenerative medicine in South Korea. Furthermore, CAR-T and TCR T-cell therapies have already revolutionized hematologic cancer treatment. With the onset of the COVID-19 pandemic, scientists are deciphering its potential against the novel coronavirus. The concept of using T cells against chronic viral infections, such as HIV and hepatitis B, has already been proposed.

Based on the previous research insights, Singapore-based Duke-NUS medical school's emerging infectious diseases research program demonstrated the utility of these immunotherapies in treating patients with COVID-19 infection.

Thus, an increase in research for use of cell therapies for COVID-19 treatment is expected to drive the market in Asian countries. In April 2021, a team of researchers from Japan used induced pluripotent stem cells (iPS) to find drugs that can effectively inhibit the coronavirus and other RNA viruses.

Key Topics Covered:

Chapter 1 Methodology and Scope

Chapter 2 Executive Summary 2.1 Market Snapshot

Chapter 3 Cell Therapy Market Variables, Trends, and Scope 3.1 Market Trends and Outlook 3.2 Market Segmentation and Scope 3.3 Market Dynamics 3.3.1 Market driver analysis 3.3.1.1 Rise in number of clinical studies for cellular therapies in Asia Pacific 3.3.1.2 Expanding regenerative medicine landscape in Asian countries 3.3.1.3 Introduction of novel platforms and technologies 3.3.2 Market restraint analysis 3.3.2.1 Ethical concerns 3.3.2.2 Clinical issues pertaining to development & implementation of cell therapy 3.3.2.2.1 Manufacturing issues 3.3.2.2.2 Genetic instability 3.3.2.2.3 Condition of stem cell culture 3.3.2.2.4 Stem cell distribution after transplant 3.3.2.2.5 Immunological rejection 3.3.2.2.6 Challenges associated with allogeneic mode of transplantation 3.3.3 Market opportunity analysis 3.3.3.1 Approval of Kymriah and Yescarta across various Asian countries 3.3.3.2 Developments in CAR T-cell therapy for solid tumors 3.3.4 Market challenge analysis 3.3.4.1 Operational challenges associated with cell therapy development & usage 3.3.4.1.1 Volume of clinical trials for cell and gene therapy vs accessible qualified centers 3.3.4.1.2 Complex patient referral pathway 3.3.4.1.3 Patient treatment, selection, and evaluation 3.3.4.1.4 Availability of staff vs volume of cell therapy treatments 3.4 Penetration and Growth Prospect Mapping for Therapy Type, 2020 3.5 Business Environment Analysis 3.5.1 SWOT Analysis; By factor (Political & Legal, Economic and Technological) 3.5.2 Porter's Five Forces Analysis 3.6 Regulatory Framework 3.6.1 China 3.6.1.1 Regulatory challenges & risk of selling unapproved cell therapies 3.6.2 Japan

Chapter 4 Cell Therapy Market: COVID-19 Impact analysis 4.1 Challenge's analysis 4.1.1 Manufacturing & supply challenges 4.1.2 Troubleshooting the manufacturing & supply challenges associated to COVID-19 4.2 Opportunities analysis 4.2.1 Need for development of new therapies against SARS-CoV-2 4.2.1.1 Role of T-cell based therapeutics in COVID-19 management 4.2.1.2 Role of mesenchymal cell-based therapeutics in COVID-19 management 4.2.2 Rise in demand for supply chain management solutions 4.3 Challenges in manufacturing cell therapies against COVID-19 4.4 Clinical Trial Analysis 4.5 Key Market Initiatives

Chapter 5 Asia Pacific Cell Therapy CDMOs/CMOs Landscape 5.1 Role of Cell Therapy CDMOs 5.2 Key Trends Impacting Asia Cell Therapy CDMO Market 5.2.1 Regulatory reforms 5.2.2 Expansion strategies 5.2.3 Rising investments 5.3 Manufacturing Volume Analysis 5.3.1 Wuxi Biologics 5.3.2 Samsung Biologics 5.3.3 GenScript 5.3.4 Boehringer Ingelheim 5.3.5 Seneca Biopharma, Inc. 5.3.6 Wuxi AppTech 5.4 Competitive Milieu 5.4.1 Regional network map for major players

Chapter 6 Asia Pacific Cell Therapy Market: Use Type Business Analysis 6.1 Market (Stem & non-stem cells): Use type movement analysis 6.2 Clinical Use 6.2.1 Market (stem & non-stem cells) for clinical use, 2017 - 2028 (USD Million) 6.2.2 Market (stem & non-stem cells) for clinical use, by therapeutic area 6.2.2.1 Malignancies 6.2.2.1.1 Market (stem & non-stem cells) for malignancies, 2017 - 2028 (USD Million) 6.2.2.2 Musculoskeletal disorders 6.2.2.3 Autoimmune disorders 6.2.2.4 Dermatology 6.2.3 Market (stem & non-stem cells) for clinical use, by cell type 6.2.3.1 Stem cell therapies 6.2.3.1.1 Market, 2017 - 2028 (USD Million) 6.2.3.1.2 BM, blood, & umbilical cord-derived stem cells/mesenchymal stem cells 6.2.3.1.3 Adipose-derived stem cell therapies 6.2.3.1.4 Other stem cell therapies 6.2.3.2 Non-stem cell therapies 6.3 Research Use

Chapter 7 Asia Pacific Cell Therapy Market: Therapy Type Business Analysis 7.1 Market (Stem & Non-stem Cells): Therapy type movement analysis 7.2 Allogeneic Therapies 7.3 Autologous Therapies

Chapter 8 Asia Pacific Cell Therapy Market: Country Business Analysis 8.1 Market (Stem & Non-stem Cells) Share by Country, 2020 & 2028

Chapter 9 Asia Pacific Cell Therapy Market: Competitive Landscape

For more information about this report visit https://www.researchandmarkets.com/r/3hdt1c

Media Contact: Research and Markets Laura Wood, Senior Manager press@researchandmarkets.com

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Asia-Pacific Cell Therapy Market8 - Opportunities in the Approval of Kymriah and Yescarta - Markets Insider

Background should not be a barrier to access stem cell transplant treatment and care – PoliticsHome

4 min read30 July

Taking account of a patients background, the circumstances of their lives and the particular challenges they might face is crucial to delivering complex treatments like stem cell transplantation.

In May, the APPG on Stem Cell Transplantation published a report following its inquiry looking at how a patients background and circumstances, including a patients geographical location, socioeconomic background and ethnicity, can lead to barriers when accessing treatment and care.

Health Inequalities, as defined by NHS England, are unfair and avoidable differences in health across the population, and between different groups within society.

Rik Basra discovered the difficulties faced by patients of an Asian background when his Acute Myeloid Leukaemia (AML) returned after a two-year remission. The only hope for Rik was a stem cell transplant but he discovered his would be an uphill battle because its less likely for patients of an ethnic minority background to have someone already on the stem cell donor register who is a genetic match to donate their stem cells for this lifesaving treatment. Unfortunately for a variety of reasons, ethnic minority patients have only a 37% chance of finding an unrelated stem cell donor, compared to 72% for white patients.

This is just one of the experiences we heard about as part of this important Inquiry. A patient shouldnt experience disparity when it comes to the best treatment and care or chance of survival and future quality of life because of their background. The inquiry has explored how ethnicity, as well as other factors such as age, where you live and your socio-economic status can impact different parts of a patients treatment and care journey when receiving a stem cell transplant. The focus has been on understanding where the barriers lie, and what can be done to remove these barriers.

We were fortunate that we were able to find a donor for Max, others were not so lucky, particularly those from mixed race and ethnic minority backgrounds

My interest in this area stems from personal experience when some 13 years ago my elder son Max was diagnosed with Leukaemia. This was devastating for my son and my family. The whole world turns upside down as you embark on a programme of treatment and the subsequent decision to go down the transplant path.

We were fortunate that we were able to find a donor for Max. We were acutely aware that others were not so lucky, particularly those from mixed race and ethnic minority backgrounds. We were again fortunate that we had a supportive family network and a job that paid well. For many the financial impact of supporting a family member through this journey is huge and rarely talked about. I have long argued that we need to look at a treatment and support plan that looks at all these factors rather than just the physical treatment itself.

We received rich and insightful responses in our inquiry from over 40 patients, family members, clinicians, charities, and researchers through written and oral evidence. What became clear was that taking account of a patients background, the circumstances of their lives and the particular challenges they might face is crucial to delivering complex treatments like stem cell transplantation.

Our report explores recommendations to address these challenges, calling on government and the NHS, amongst others, to make changes such as investing in research and making sure care is culturally appropriate, meaning healthcare professionals have the ability to understand, communicate with and effectively interact with people across cultures. We were joined by Lord Bethell, a Health Minister with responsibility for stem cell transplantation, at the report launch. He commented on timeliness of this report and welcomed the recommendations made, citing a commitment for the Department to work with APPG on the recommendations.

We hope the findings from this report will act as a springboard to encourage more research and a renewed focus on understanding and overcoming barriers to accessing treatment and care for a stem cell transplant.

Our findings and our recommendations will be relevant far beyond stem cell transplantation. Its vital we use the lessons from the pandemic to make a real step-change in health inequalities. We have a once in a lifetime opportunity to ensure patients get the treatment, care and support they need whatever their background. Find out more about the inquiry here.

Mark Tamiis the Labour MP for Alyn and Deeside and chair of theAPPG on Stem Cell Transplantation.

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Background should not be a barrier to access stem cell transplant treatment and care - PoliticsHome

Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of FT819, the First-ever iPSC-derived CAR T-Cell Therapy |…

Details Category: DNA RNA and Cells Published on Tuesday, 03 August 2021 10:03 Hits: 755

Off-the-Shelf CAR T-cell Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

Phase 1 Clinical Study will Evaluate Three Dosing Regimens of FT819 for Patients with Advanced B-cell Leukemias and Lymphomas

SAN DIEGO, CA, USA I August 02, 2021 I Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, announced today that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement.

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics haslicensedintellectual propertyfrom MSK on which Dr. Sadelain is aninventor.As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics iPSC Product Platform The Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819 FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

SOURCE: Fate Therapeutics

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Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of FT819, the First-ever iPSC-derived CAR T-Cell Therapy |...

Gliomagenesis is orchestrated by the Oct3/4 regulatory network. – Physician’s Weekly

Glioblastoma multiforme (GBM) is a lethal brain tumor characterized by developmental hierarchical phenotypic heterogeneity, therapy resistance and recurrent growth. Neural stem cells (NSCs) from human central nervous system (CNS), and glioblastoma stem cells from patient-derived GBM (pdGSC) samples and cultured in both 2D well-plate and 3D monoclonal neurosphere culture system (pdMNCS). The pdMNCS model shows promise to establish a relevant 3D-tumor environment that maintains GBM cells in the stem cell phase within suspended neurospheres. Utilizing the pdMNCS, we examined GBM cell-lines for a wide spectrum of developmental cancer stem cell markers, including the early blastocyst inner-cell mass (ICM)-specific Nanog, Oct3/4,B, and CD133. We observed that MNCS epigenotype is recapitulated using gliomasphere-derived cells. CD133, the marker of GSC is robustly expressed in 3D-gliomaspheres and localized within the plasma membrane compartment. Conversely, gliomasphere cultures grown in conventional 2D culture quickly lost CD133 expression, indicating its variable expression is dependent on cell-culture conditions. Critically, this experiment demonstrates incomplete differentiation of cytoskeleton microtubules and intermediate filaments (IFs) of patient derived cells, similar to commercially available GBM cell lines. Subsequently, in order to determine whether Oct3/4 it was necessary for CD133 expression and cancer stemness, we transfected 2D and 3D culture with siRNA against Oct3/4 and found a significant reduction in gliomasphere formation. These results suggest that expression of Oct3/4,Aand CD133 suppress differentiation of GSCs.

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Gliomagenesis is orchestrated by the Oct3/4 regulatory network. - Physician's Weekly

Fate Therapeutics Reports Second Quarter 2021 Financial Results and Highlights Operational Progress – StreetInsider.com

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First Patient Treated for Relapsed / Refractory ALL in Landmark Phase 1 Clinical Trial of FT819, the First-ever iPSC-derived CAR T-cell Therapy; Off-the-Shelf Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

FT516 Interim Phase 1 Data for Relapsed / Refractory Lymphoma Featured at ASCO; 8 of 11 Patients in Dose Cohorts 2 and 3 Achieved Objective Response, including 6 Patients with Complete Response

Interim Phase 1 Data from FT516 and FT538 Programs for Relapsed / Refractory AML Highlighted at May Investor Event; 5 of 12 Patients Achieved Objective Response with Complete Clearance of Bone Marrow Leukemic Blasts

New Phase 1 Clinical Data from FT516 and FT596 Programs in Relapsed / Refractory Lymphoma to be Featured at Investor Event on August 19

SAN DIEGO, Aug. 04, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, today reported business highlights and financial results for the second quarter ended June 30, 2021.

We are very pleased with the early clinical safety and activity we have observed with our off-the-shelf, iPSC-derived NK cell programs in relapsed / refractory lymphoma and acute myeloid leukemia, where interim Phase 1 data indicate FT516 and FT538 are well tolerated and can deliver complete responses for patients. We look forward to sharing additional clinical data from our FT516 and FT596 programs in B-cell lymphoma at our upcoming investor event, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Additionally, treatment of the first patient with FT819, the first-ever iPSC-derived T-cell therapy to undergo clinical investigation, is a landmark achievement and further demonstrates the Companys leadership in off-the-shelf, iPSC-derived cell therapy and the versatility of its proprietary iPSC Product Platform.

B-cell Malignancy Disease Franchise

AML Disease Franchise

Multiple Myeloma Franchise

Solid Tumor Franchise

Other Corporate Highlights

Second Quarter 2021 Financial Results

Today's Conference Call and WebcastThe Company will conduct a conference call today, Wednesday, August 4, 2021 at 5:00 p.m. ET to review financial and operating results for the quarter ended June 30, 2021. In order to participate in the conference call, please dial please dial 800-773-2954 (toll free) or 847-413-3731 (toll) and refer to conference ID 50196101. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company's website at http://www.fatetherapeutics.com. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About Fate Therapeutics iPSC Product Platform The Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516 FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT596 FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About FT538 FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636).

About FT819 FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Companys results of operations, financial condition and sufficiency of its cash and cash equivalents to fund its operations, as well as statements regarding the advancement of and plans related to its product candidates, clinical studies and preclinical research and development programs, the Companys progress, plans and timelines for the manufacture and clinical investigation of its product candidates, the timing for the Companys receipt of data from its clinical trials and preclinical studies, the initiation of additional clinical trials and additional dose cohorts in ongoing clinical trials of the Companys product candidates and the submission of IND applications for additional programs, the Companys development and regulatory strategy, the therapeutic and market potential of the Companys product candidates, and the parties rights and obligations under the Companys collaboration agreements. These and any other forward-looking statements in this release are based on management's current expectations of future events 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 the Companys product candidates may not demonstrate the requisite safety or efficacy to achieve regulatory approval or to warrant further development, the risk that results observed in prior studies of the Companys product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Companys product candidates or in the initiation of, or enrollment of patients in, any clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Companys ongoing and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), risks related to the impact of the COVID-19 pandemic on various aspects of the Companys business and operations, including its ability to initiate, conduct and complete its clinical trials, and the risk that the Companys expenditures may exceed current expectations for a variety of reasons. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Availability of Other Information about Fate Therapeutics, Inc. Investors and others should note that the Company routinely communicates with investors and the public using its website (www.fatetherapeutics.com) and its investor relations website (ir.fatetherapeutics.com) including, without limitation, through the posting of investor presentations, SEC filings, press releases, public conference calls and webcasts on these websites. The information posted on these websites could be deemed to be material information. As a result, investors, the media, and others interested in Fate Therapeutics are encouraged to review this information on a regular basis. The contents of the Companys website, or any other website that may be accessed from the Companys website, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.

Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands, except share and per share data) (unaudited)

Condensed Consolidated Balance Sheets (in thousands) (unaudited)

Contact: Christina Tartaglia Stern Investor Relations, Inc. 212.362.1200 christina@sternir.com

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Fate Therapeutics Reports Second Quarter 2021 Financial Results and Highlights Operational Progress - StreetInsider.com

Improving the Treatment Gap in Diffuse Large B-Cell Lymphoma – Targeted Oncology

Gilles Salles, MD, discusses the need for new therapies to treat diffuse large B-cell lymphoma.

Gilles Salles, MD, the lymphoma service chief at Memorial Sloan Kettering Cancer Center, discusses the need for new therapies to treat diffuse large B-cell lymphoma (DLBCL).

According to Salles, once patients fail primary therapy, limited options remain. For approximately 50% of the patient population, those with limited comorbidities or those under a certain age, the standard of care is salvage chemotherapy followed by stem cell transplant.

However, for the approximately half of patients who are not eligible for this route, the treatment is usually immuno-chemotherapy, according to Salles. For most regimens, the response rate is limited. For patients who do respond, the duration of response (DOR) is typically only between 4 to 6 months. The median survival after the second-line therapy is about a year.

News agents have made progress in this space. For example, chimeric antigen receptor T cells show promise, but eligibility and access remain a major hurdle for many patients. New agents are also in the pipeline, though according to Salles, many have a short DOR.

Excerpt from:
Improving the Treatment Gap in Diffuse Large B-Cell Lymphoma - Targeted Oncology

MUHS, Nashik to conduct fellowship course in regenerative medicine – BSI bureau

Maharashtra University Of Health Sciences (MUHS), Nashik has been granted first affiliations to conduct a fellowship course in regenerative medicine and stem cell-based therapies on a research basis at Dr Mahajans Hospital & Stem Rx Bioscience Solution, Navi Mumbai. The move will address the education and training gaps in this new area of regenerative medicine.

MD/MS/M.Ch,/DM/DNB qualified surgeons/physicians/super specialists from allopathy, undergraduate or postgraduate degrees equivalent to and recognised by the Medical Council of India are eligible for admission.

Candidates should have six months of basic molecular biological background in basic research. The basic research in molecular biology of human body science is the first time in India to give research background to qualified physicians and surgeons to practice medicine.

The two-year fellowship programme will have FDA regulations, ethics, emerging technologies in stem cell, pre-clinical studies, mesenchymal stem cell isolation and transplantation, etc

Dr Pradeep Mahajan, Regenerative Medicine Researcher, StemRx Bioscience Solutions, Navi Mumbai said, The fellowship course has been designed to ensure that qualified individuals get the required theoretical training as well as practical exposure to learn the intricacies of research in the field of RM. Candidates will be able to pursue their research in this field and contribute to the ever-increasing need for novel therapeutic technologies. It would improve the practice of regenerative and cellular medicine and hopefully obviate the need for regulatory action in some cases.

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MUHS, Nashik to conduct fellowship course in regenerative medicine - BSI bureau

FDA Hands Out Surprising Rejection of Meduxus and Medac’s Treosulfan – BioSpace

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Medexus Pharmaceuticals and medacGmbHreceiveda Complete Response Letter (CRL) from the Food and Drug Administration (FDA) for its New Drug Application (NDA) for treosulfan. The drug was being submitted for use in combination with fludarabine as a preparation for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The companies had a target action date of August 11.

A preparative regimen is given to the patient before stem cell transplantation with the goal of decreasing the tumor burden. And in the case of allogeneic transplantation, it allows for engraftment of the donor cells.

The CRL indicated that it couldn't be approved in its present form. It offered specific recommendations, including additional clinical and statistical data related to the primary and secondary endpoints of the pivotal Phase III trial. The companies say they are reviewing the CRL to decide on a course of action.

Ken d'Entremont, chief executive officer of Medexus, said, "Given the recent Health Canada approval, European Medicines Agency approval in 2019, as well as supporting data from more than 100 publications, we were all surprised by the FDA's response."

"That being said, Medexus and medac look forward to continuing to work with the FDA to address their requests in a timely manner, and we remain optimistic for a future, albeit delayed, approval of treosulfan in the United States, complete with Orphan Drug Designation."

He went on to say that the current standard of care "is not suitable for numerous at-risk groups, due to the high toxicity effects, and treosulfan has demonstrated excellent survival data among those groups."

Medexus, headquartered in Toronto, Ontario, Canada, and medac, based in Wedel, Germany,inkeda licensing deal on July 12 to commercialize treosulfan in Canada. It is being marketed in Canada under the name Trecondyv. Medexus will handle sales and marketing, while medac will handle manufacturing and supply.

The therapy has been distributed in Canada under the Special Access Program and recently received approval for commercialization from Health Canada for adults with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) who are at increased risk for standard conditioning therapies. It was also approved for children older than one-year-old with AML or MDS.

At the time, Magnus Kuster, vice president of International Sales & Regions for medac, noted, "The treosulfan-based conditioning regimen stands out for its combination of being highly effective similar to the potency of myeloablative procedures while simultaneously exhibiting significantly reduced toxicity. We at medac are very proud of our first-in-class conditioning agent as it fully meets our company's goals of improving patients' lives and supporting healthcare professionals in the best possible way."

In response to the CRL, Meduxus's general manager of U.S. Operations, Michael Adelman, said, "We are disappointed with the immediate result, but are encouraged by an incredible amount of support from key opinion leaders and the medical community for use of treosulfan in the United States. With the extensive launch preparations we have taken to date, we are well positioned to meet the expected strong demand for treosulfan."

They will work with the FDA to address the issues in the CRL while ready to trigger their U.S. marketing plan when it gets approved.

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FDA Hands Out Surprising Rejection of Meduxus and Medac's Treosulfan - BioSpace

Dr. Flowers on Efforts to Improve Frontline Treatment in DLBCL – OncLive

Christopher Flowers, MD, discusses efforts to improve the frontline standard of care in diffuse large B-cell lymphoma.

Christopher Flowers, MD,department chair, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses efforts to improve the frontline standard of care in diffuse large B-cell lymphoma (DLBCL).

The frontline standard of care therapy has not changed significantly over the past 20 years in DLBCL, Flowers says. In the early 2000s, it was observed that the addition of rituximab to standard CHOP (R-CHOP) therapy improved survival for elderly patients with DLBCL compared with CHOP alone, Flowers explains.

Although several research efforts have attempted to improve upon frontline R-CHOP, no survival advantages have been demonstrated, Flowers says. For example, randomized phase 3 trials evaluating intensified treatment approaches, stem cell transplantation, and the addition of novel agents, including bortezomib (Velcade), lenalidomide (Revlimid), and ibrutinib (Imbruvica), have been reported without demonstrating improvement vs R-CHOP in most patients with DLBCL, Flowers concludes.

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Dr. Flowers on Efforts to Improve Frontline Treatment in DLBCL - OncLive