Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

The therapy modifies patients’ T cells to carry an anti-CD7 CAR and re-administers them. Credit: Kateryna Kon/Shutterstock. Singapore’s National University Health System (NUHS) has announced that a new cluster of differentiation (CD7) chimeric antigen receptor (CAR)-T cell therapy has demonstrated significant potential in treating patients with relapsed or refractory T-cell acute lymphoblastic leukaemia (T-ALL), offering hope to those who have exhausted standard treatments. The National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine) and the NUHS developed the cell therapy, which targets CD7 on leukaemia cells. This fratricide-resistant therapy was administered to 17 patients at the NUH in Singapore and at the Ospedale Pediatrico Bambino Gesù in Rome, Italy, from April 2019 to October 2023. The patients, aged between two and 72 years, had T-ALL that was resistant to chemotherapy or had relapsed post-treatment. Utilising technology in Professor Dario Campana’s laboratory under the Department of Paediatrics at NUS Medicine, the therapy involved reprogramming patients’ own T cells to express an anti-CD7 CAR, which was then re-infused into the patients. See Also: EMA starts review into hair loss drugs about potential link to suicidal thoughts ProductLife boosts drug development with IntiQuan acquisition The re-engineered CAR T-cells attack T-leukaemia cells that present the CD7 protein on their surface. Remarkably, 16 out of the 17 patients were observed to achieve complete remission within one month, as confirmed by ultra-sensitive flow cytometry tests capable of detecting one leukaemia cell among 10,000 normal cells. The tests were developed by Ms Elaine Coustan-Smith’s laboratory at NUS Medicine and were instrumental in assessing CD7 expression in leukaemic cells to determine the eligibility of patients and monitor the CAR-T cells post-infusion. The first patient to receive this treatment has maintained remission for five years without the need for further chemotherapy or a bone marrow transplant. Despite the high tumour burden and extensive prior treatment of the patients, the therapy was well-tolerated with mild side effects. The study’s first author, Khoo Teck Puat of the National University Children’s Medical Institute (KTP-NUCMI), NUH, and Paediatric Haematology and Oncology Division consultant Dr Bernice Oh stated: “This CAR-T therapy is a new and promising tool to treat T-ALL patients who have failed conventional treatment. “These patients had exhausted all potentially curative options, and we are heartened that we could give them another clear chance at cure without severe side effects. We are committed to seeking better cures for patients with complex and treatment-resistant cancers.” Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

BOSTON--(BUSINESS WIRE)-- #Biotech -- Odyssey Therapeutics, Inc. , a biotechnology company pioneering next-generation precision immunomodulators for inflammatory diseases, today announced the formation of its Scientific Advisory Board (SAB), which includes renowned experts in the fields of immunology and therapeutic development. The SAB will be chaired by Stephen Blacklow, M.D., Ph.D., who holds positions at Harvard Medical School and the Dana- Farber Cancer Institute and is a recognized drug discovery innovator. “The lens by which we evaluate therapeutic opportunities is supported by the profound knowledge of immune biology among our team and trusted advisors,” said Gary Glick, Ph.D., founder and CEO of Odyssey Therapeutics. “We are fortunate to work with a group of preeminent scientific minds and recognized drug hunters with extensive track records in developing molecules that have successfully translated from scientific hypothesis to clinical validation and regulatory success. We look forward to benefiting from their collective experience as we move our lead programs into the clinic and advance our earlier-stage pipeline.” Dr. Blacklow commented, “I am excited to work alongside Gary, my esteemed SAB members and the Odyssey team. Odyssey’s differentiated approach and dedication to advancing medicines for inflammatory disease is inspiring, and I look forward to contributing my expertise to help drive these groundbreaking programs forward.” Odyssey’s SAB is comprised of the following members: Dr. Blacklow, M.D., Ph.D., Gustavus Adolphus Pfeiffer Professor and Department Chair of Biological Chemistry and Molecular Pharmacology at Harvard Medical School, member of the Department of Cancer Biology at the Dana-Farber Cancer Institute: Dr. Blacklow is a globally recognized expert in signal transduction at the structural and molecular level. His research on the Notch pathway, a complex signaling pathway integral to immune cell function, has led to the development of multiple investigational therapies for hematologic malignancies, such as T cell acute lymphocytic leukemia. Of his many awards and affiliations, Dr. Blacklow received the National Cancer Institute’s prestigious Outstanding Investigator Award in 2017, and was elected to the Association of American Physicians in 2018 and the American Academy of Arts and Sciences in 2024. He received his M.D. and Ph.D. degrees from Harvard University. Robert Abraham, Ph.D., former Executive Vice President of Cancer Biology at Odyssey: Dr. Abraham previously served as Chief Scientific Officer at Vividion Therapeutics, which was acquired in August 2021 by Bayer for $2 billion. He has extensive experience in both the pharmaceutical industry and academia, including 10 years at Pfizer where he served as Senior Vice President and group head in Oncology Research and Development, with oversight of cancer drug discovery and early clinical development. He previously held roles at Duke University Medical Center, including an Endowed Chair in the Department of Cancer Biology. Throughout his career, he has made significant contributions to multiple research areas, including cell signaling, T lymphocyte biology, rapamycin pharmacology and mTOR functions, cancer metabolism and DNA damage responses. He received a B.S. in biology from Bucknell University and a Ph.D. in pharmacology from the University of Pittsburgh. Richard Flavell, Ph.D., F.R.S., Sterling Professor of Immunobiology, Yale School of Medicine, and Investigator, Howard Hughes Medical Institute: Dr. Flavell is a co-discoverer of introns in cellular genes, and his research focuses on the molecular and cellular mechanisms that govern immune responses, from the characterization of signal transduction pathways to the regulation of immune cell differentiation and activation. His work has been instrumental in identifying key components of the innate immune system, such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs), and activation of the innate immune system and inflammatory disease. He received his B.Sc. and Ph.D. in biochemistry from the University of Hull, England. Alexander (Sasha) Rudensky, Ph.D., Director, Ludwig Center for Cancer Immunotherapy, Tri-Institutional Professor at Memorial Sloan Kettering Cancer Center, The Rockefeller University and Cornell University, and Investigator, Howard Hughes Medical Institute: Dr. Rudensky’s research has defined regulatory T cells and the roles they play in autoimmunity, tolerance, allergic disease, infections and cancer. His current work addresses the molecular mechanisms underlying regulatory T cell activity, and the role these cells play in autoimmunity, tumor immunity and immunity to infections. He received his candidate of sciences degree from the Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow, and completed his postdoctoral work at the Yale School of Medicine. Ruslan Medzhitov, Ph.D., Sterling Professor, Yale University School of Medicine and Investigator, Howard Hughes Medical Institute: Dr. Medzhitov’s work has identified innate immune sensing pathways and established the principle of innate control of adaptive immunity. His current research is focused on inflammation biology, allergic diseases and evolutionary medicine. Dr. Medzhitov has been a recipient of numerous awards and honors, including the 2019 Dickson Prize in Medicine. He earned his Ph.D. from Moscow State University. Sun Hur, Ph.D., Professor at Harvard Medical School and Boston Children’s Hospital and Investigator, Howard Hughes Medical Institute: Dr. Hur’s work on the molecular mechanisms of how the immune system distinguishes between self and non-self-entities led to the discovery of MDA5 and its role in innate immunity, autoimmunity and autoinflammatory diseases. She is a past recipient of the Vilcek Prize for Creative Promise in Biomedical Science for her research on inflammatory and autoimmune diseases and experimental enzymology. She earned her B.Sc. from Ewha Womans University and her Ph.D. in physical chemistry from the University of California, Santa Barbara. Seth Masters, Ph.D., Centre Head, Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research: Dr. Masters’ research on understanding the innate immune pathways that drive diseases led to the identification of the mechanisms by which NLRP1 mediates autoinflammatory disease. His current research explores how innate immune pathways contribute to inflammatory bowel disease, asthma, metabolic diseases and neurodegeneration. Dr. Masters obtained his B.Sc. in biochemistry from The University of Melbourne, Australia, and his Ph.D. in medical biology from the Walter and Eliza Hall Institute. Michael B. Yaffe, M.D., Ph.D., Professor of Biology and Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology: Dr. Yaffe’s research focuses on uncovering signaling pathways in cells that respond to stress, DNA damage and inflammatory cytokines and how the outputs of these pathways are integrated at the molecular and systems level to control the cell outcomes. Dr. Yaffe received his B.S. in materials science and engineering from Cornell University, M.D., Ph.D. degrees from Case Western Reserve University and advanced postdoctoral training with Prof. Lew Cantley at Harvard Medical School. About Odyssey Therapeutics Odyssey Therapeutics is a clinical-stage biotechnology company focused on discovering, developing and commercializing the next generation of inflammatory precision medicines. Since its founding in 2021, Odyssey has rapidly advanced a pipeline of clinical- and research-stage programs, leveraging the scientific expertise of its team of drug hunters and a comprehensive suite of tools to tackle drug targets with the greatest potential to benefit patients. Odyssey’s mission is to create extraordinary leaps in patient outcomes and change the standard of care for those living with serious inflammatory diseases. For more information, please visit odysseytx.com and follow Odyssey Therapeutics on X (formerly Twitter) and LinkedIn . Contacts Josh George jgeorge@spectrumscience.com 713-828-1913

Genetic changes in non-coding DNA impacts outcomes PHILADELPHIA and MEMPHIS, Tenn., Aug. 14, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP), St. Jude Children's Research Hospital (St. Jude) and the Children's Oncology Group (COG) today announced a significant paradigm shift in the understanding of T-lineage acute lymphoblastic leukemia (T-ALL), an aggressive and high-risk form of cancer, to one frequently driven by genetic changes in non-coding portions of our DNA. The collaborative study, supported by the Gabriella Miller Kids First Pediatric Research Program (Kids First) and National Institutes of Health (NIH) Common Fund, was published today in the journal Nature. Continue Reading St. Jude Logo David T. Teachey, MD, is an attending physician, Director of Clinical Research at the Center for Childhood Cancer Research at CHOP and Chair of the Acute Lymphoblastic Leukemia disease committee in the Children's Oncology Group. Charles Mullighan, MBBS, MD, St. Jude Children's Research Hospital, Comprehensive Cancer Center deputy director and Department of Pathology member Many children, adolescents, and young adult patients with T-ALL traditionally respond well to initial treatment. However, patients who relapse or have treatment-resistant disease often face a dire prognosis. Given the aggressive nature and rapid progression of the disease, and limited understanding of the genetic basis of T-ALL, researchers saw an urgent need for new and effective approaches to diagnosis and treatment. "This paper is the first to transcend previous barriers and comprehensively profile the whole genome, uncovering critical insights in more than 1,300 children, adolescents and young adults with T-ALL," said David T. Teachey, M.D., an attending physician, Director of Clinical Research at the Center for Childhood Cancer Research at CHOP and Chair of the Acute Lymphoblastic Leukemia disease committee in the COG. "These findings are a significant clinical advancement, as the goal in treating T-ALL is to prevent relapse, which requires identifying the patients most at risk. This data now makes it possible to risk stratify patients with T-cell leukemia, identifying those with a high-risk of relapsing so we can treat them with newer or alternative medicines." Prior studies were unable to identify important genetic changes in T-ALL, as they focused on the coding genome, the part of DNA that encodes proteins, the building blocks of cells. However, only 1% of DNA is coding, while the other 99% is termed non-coding. Once considered useless, scientists now recognize that the non-coding region plays a key role in regulating biological processes. It signals the cell when to produce certain proteins, like a crossing guard aiding people to safely cross the street. In this case, researchers studied more than 1,300 patients treated on the COG AALL0434 clinical trial and sequenced both the tumor and non-tumor genomes of each patient. While the researchers previously suspected that non-coding DNA in T-ALL played an important role, this study's findings are the first ever to establish that at a large scale. The study found that approximately 60% of the genetic changes driving T-ALL cancer cells are non-coding changes. This fundamentally alters the way researchers think about T-ALL, offering a better understanding of disease biology. This leads to innovative treatments, including new immunotherapies developed at CHOP and St. Jude. Traditionally, patients with T-ALL have been categorized by risk based on their therapy response and immunophenotype, which profiles cell surface proteins as part of the diagnostic workup. While cell surface protein expression helps define T-ALL subtypes, it hasn't proven effective in consistently identifying which patients have a good prognosis. The new comprehensive data revealed why, strongly suggesting that a genomic approach replace the current immunophenotypic classification. As a result, the researchers developed models that incorporate genetics and response to treatment to risk stratify patients with T-ALL accurately and are currently in the process of validating results using patient samples from the next COG trial of T-ALL. "It was striking how abundant these non-coding changes were and how many of them were enhancer perturbation events, whether it was hijacking or co-option of an existing enhancer, or changes that generated a new enhancer," said Charles Mullighan, MBBS, MD, St. Jude Children's Research Hospital, Comprehensive Cancer Center deputy director and Department of Pathology member. "We now have a much stronger framework to take these alterations back to the lab and say now we've got better information to build the right models to understand the biology, and then to test therapy. We have very clear information that these are the sorts of alterations that people need to focus on to build a diagnostic test." Researchers were able to classify T-ALL into 15 subtypes with distinct gene expression and genomic drivers, including previously undefined subtypes. They refined the classification of known subtypes and showed that driver lesions, other genetic changes, and the original cell type work together to define the genomic subtype and the clinical and biological characteristics of a condition. They also observed a significant link between the type of gene alterations and outcomes in T-ALL. This new observation shows it is not only which gene is altered in the cancer cells, but also how it is altered, that helps define prognosis and chance of a cure. "Future research must continue to determine broader applications for this approach," said Teachey. "These findings offer a strong a roadmap for improving patient outcomes and curing more children and adults with T-ALL." In addition to the Gabriella Miller Kids First Pediatric Research Program and National Institutes of Health (NIH) Common Fund, the study was supported by the Leukemia and Lymphoma Society, Alex's Lemonade Stand Foundation, Hyundai Hope on Wheels, the COG Foundation, ALSAC, the fundraising and awareness organization of St. Jude, and private donations from patients and families, including the Harrison Willing Memorial Research Fund, the Invisible Prince Foundation, and the Aiden Everett Davies Innovation Fund. Polonen, et al. "The genomic basis of childhood T-lineage acute lymphoblastic leukemia." Nature. Online August 14, 2024. DOI:10.1038/s41586-024-07807-0 . About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . About St. Jude Children's Research Hospital St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read St. Jude Progress, a digital magazine, [] and follow St. Jude on social media at @stjuderesearch. Contact: Jennifer Lee Children's Hospital of Philadelphia (267) 426-6084 [email protected] Contact: Gary Bridgman St. Jude Children's Research Hospital Desk: (901) 595-2028 [email protected] [email protected] SOURCE Children's Hospital of Philadelphia; St. Jude Children’s Research Hospital