SUV39H1

Study shows that ablating the histone methyltransferase SUV39H1 enhances T cell memory/persistence, reduces T cell exhaustion, and provides protection against tumor relapses in mouse models PARIS, Nov. 7, 2023 /PRNewswire/ -- Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, has announced a new preclinical study showing that CAR T cell memory differentiation and persistence can be enhanced by inactivating SUV39H1, an enzyme (histone methyltransferase) that epigenetically regulates and represses memory-associated genes. The paper, published in Cancer Discovery, is titled "SUV39H1 Ablation Enhances Long-Term CAR-T Function in Solid Tumors." In this preclinical study, researchers at Mnemo and its strategic academic collaborator Institut Curie demonstrated that genetic ablation of histone methyltransferase SUV39H1 reprograms human T cells to express genes associated with memory and stemness (the capability of a cell for self-renewal and differentiation) and to reduce expression of genes associated with T cell exhaustion, which can cause cell therapies to lose their effectiveness over time, resulting in reduced efficacy and tumor relapse. SUV39H1-inactivated CAR T cells promote long-term protection against tumor relapses and rechallenges, demonstrated in mouse models of lung cancer and other solid tumors. "T cell exhaustion and lack of persistence impede the long-term success of immunotherapy treatments for tumors," said Mnemo Chief Executive Officer Robert LaCaze. "This study shows that inactivating SUV39H1 opens the path to the development of novel therapeutics addressing these challenges with the goal of preventing tumor relapse with immunotherapies." "This work moves us toward a deeper understanding of the importance of SUV39H1 inactivation in improving T cell persistence and longevity of treatment success," said Sebastian Amigorena, Chief Scientific Officer at Mnemo and senior author on the paper. "Mnemo is grateful to our academic partners, whose collaboration made this rigorous and illuminating study possible. These promising findings are a result of our combined expertise and resources." Reference: S. López-Cobo, J.R. Fuentealba, P. Gueguen, P.E. Bonté, K. Tsalkitzi, I. Chacón, S. Glauzy, A. Bohineust, A. Biquand, L. Silva, Z. Gouveia, C. Goudot, F. Perez, M. Saitakis and S. Amigorena. SUV39H1 Ablation Enhances Long-Term CAR-T Function in Solid Tumors. Cancer Discovery. 2023 November. About Mnemo Therapeutics Mnemo is driven to create powerful immunotherapies to improve the body's ability to detect and eradicate cancer. A lack of cancer-specific targets, coupled with lack of long-term persistence and sensitivity, create significant challenges in the field of immuno-oncology. Mnemo is committed to addressing these problems and engineering the future of immunotherapies to transform the lives of people with cancer through the discovery of novel cancer-specific targets, while boosting immune activity to treat solid tumors. Mnemo's state of the art laboratories are located in Paris. To learn more, visit and follow Mnemo Therapeutics on X (@MnemoTx) and LinkedIn. SOURCE Mnemo Therapeutics

PARIS, July 6, 2022 /PRNewswire/ -- Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, today announced a publication in Nature Communications demonstrating that the histone lysine methyltransferase enzyme Suv39h1 plays not only a key role in T cell persistence, but also in T cell activation and exhaustion. This research was conducted at Institut Curie between the lab of Sebastian Amigorena, Ph.D., CNRS research director, head of the Immune Responses and Cancer Team (Immunity and Cancer Unit – Institut Curie/Inserm) and scientific co-founder of Mnemo, and the lab of Eliane Piaggio, Ph.D., Inserm research director and head of the Translational Immunotherapy Team (Immunity and Cancer Unit, Institut Curie/Inserm). "T cell exhaustion and lack of persistence are two key challenges that hinder effective and durable immunotherapy treatments for tumors," said Mnemo Chief Executive Officer, Robert LaCaze. "Through Suv39h1 inactivation, Mnemo aims to create therapies with increased durability and activity." Previous research, exclusively licensed to Mnemo from the lab of Dr. Amigorena, demonstrated that Suv39h1 is a key enzyme involved in the epigenetic regulation of immune cell memory, and that deletion of Suv39h1 results in increased immune cell memory and more durable therapeutic responses. The research demonstrated in the Nature publication goes on to show that this enzyme is a key factor in regulating T cell exhaustion. "As is known, the potency of current treatments such as immune checkpoint inhibitors (i.e. anti-PD-1) is limited by repeated stimulation of T cells in a tumor rich environment, resulting in T cell exhaustion," said Dr. Amigorena. "The current study showcases that Suv39h1 acts as an epigenetic checkpoint inhibitor that, when coupled with anti-PD-1 treatment, results in increased T cell activity and decreased T cell exhaustion." Key takeaways from the study include: Suv39h1 KO CD8+ T cells are more responsive to T-cell receptor (TCR) activation and become highly cytolytic following PD-1 blockade, resulting in increased tumor killing potency. Deletion of Suv39h1 resulted in higher CD8+ T cell tumor infiltration when coupled with anti-PD-1 treatment. CD8+ T cells in Suv39h1 KO mice treated with anti-PD-1 displayed the highest level of a protease (GZMb) responsible for T cell induced apoptosis of tumor cells, despite displaying elevated levels of biomarkers associated with exhaustion. Suv39h1 deletion resulted in increased chromatin accessibility in regions responsible for immune cell signaling and cytotoxicity during anti-PD-1 treatment, compared to WT with anti-PD-1 treatment. Inhibition of Suv39h1 via small molecules mimicked Suv39h1 deletion in mouse models, reinforcing that this enzyme is playing a direct role in T cell activity. "Limited potency, durability, and cancer-specific targets impede the efficacy of current immunotherapies, leading to off-target side effects and patient relapse," said Mnemo Co-Founder and Chief Operating Officer, Alain Maiore. "Alongside our EnfiniT Discovery Engine that identifies novel cancer targets, this research demonstrates Mnemo's commitment to addressing multiple bottlenecks in the efficacy of immunotherapy, as well as bringing solutions to patients." References: CD8+T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas. Leticia Laura Niborski, Paul Gueguen, Mengliang Ye, Allan Thiolat, Rodrigo Nalio Ramos, Pamela Caudana, Jordan Denizeau, Ludovic Colombeau, Raphaël Rodriguez, Christel Goudot, Jean-Michel Luccarini, Anne Soudé, Bruno Bournique, Pierre Broqua, Luigia Pace, Sylvain Baulande, Christine Sedlik, Jean-Pierre Quivy, Geneviève Almouzni, José L. Cohen, Elina Zueva, Joshua J. Waterfall, Sebastian Amigorena & Eliane Piaggio. About Mnemo Therapeutics Mnemo is developing transformational immunotherapies to improve the body's ability to fight and overcome cancer. Integral to Mnemo's approach is the EnfiniT Discovery Engine, composed of key technologies that work to identify novel cancer-specific antigens and enhance immune cells' memory and persistence. Mnemo will harness these technologies with multiple modalities across a range of oncology indications, engineering the future of immunotherapies to transform the lives of people with cancer. Mnemo is headquartered in Paris with an office in New York City, and it maintains state of the art laboratories in Paris, New York, and Princeton, New Jersey. The company leverages an international talent pool and global resources in its quest to create immunological cures. To learn more, visit and follow Mnemo Therapeutics on Twitter (@MnemoTx) and LinkedIn. SOURCE Mnemo Therapeutics

PARIS, June 13, 2022 /PRNewswire/ -- Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, today announced the kick-off of their participation in the prestigious Hospital-University Research in Health (RHU) program. Designed by France's National Research Agency, the RHU funding supports cutting-edge research and cross-institutional collaborations, bringing together academia, businesses, and hospitals to push the boundaries of what is possible in healthcare. In December of 2021, 17 proposals were selected for the RHU funding. Among them, receiving close to 10 million euros, is the EpCART project. Under the leadership of Sebastian Amigorena, Ph.D., one of Mnemo's scientific co-founders and head of the Immune Responses and Cancer Team at Institut Curie, the EpCART project aims to clinically validate a novel approach to CAR-T immunotherapy. "We are honored to be named a laureate for this prestigious initiative and work alongside our long-standing partners at Institut Curie, as well as the MEARY Cell and Gene Therapy Center at Saint-Louis Hospital, AP-HP," said Mnemo CEO, Robert LaCaze. The EpCART project focuses on epigenetic reprogramming of CAR-T cells. Through the inactivation of SUV39H1, a key enzyme in the differentiation pathway of T cells, the memory phenotype of these cells can be greatly increased. This works to achieve long-lasting tumor control, addressing patient relapse. "Current immuno-oncology therapies often suffer from immune-cell memory loss, causing therapies to become less active and persistent in their ability to attack cancer cells over time," said Dr. Amigorena. "The EpCART project mines insights into the memory of the immune system to overcome this challenge and produce a new class of CAR-T therapies with enhanced memory and persistence. We believe this will drive more durable responses for cancer patients." Over the next five years, the EpCART project will seek to clinically validate this technology as an autologous therapy. Mnemo will work in collaboration with the other EpCART partners to conduct a Phase I-II clinical trial, investigating the activity of these innovative CAR-T therapies in a cohort of 35 patients with difficult-to-treat solid tumors. The EpCART project will accelerate research on Mnemo's EnfiniT Discovery Engine, an integrated drug discovery tool combining key technologies to create lasting immune memory, identify novel cancer-specific targets, and more. "Today is an exciting step in our journey to develop transformational immunotherapies with the aim of improving the body's ability to detect, fight, and overcome cancer," said Mnemo Co-Founder and Chief Operating Officer, Alain Maiore. "We are truly honored to collaborate with such esteemed partners and look forward to the fruits of this initiative." About Mnemo Therapeutics Mnemo is developing transformational immunotherapies to improve the body's ability to fight and overcome cancer. Integral to Mnemo's approach is the EnfiniT Discovery Engine, composed of key technologies that work to identify novel cancer-specific antigens and enhance immune cells' memory and persistence. Mnemo will harness these technologies with multiple modalities across a range of oncology indications, engineering the future of immunotherapies to transform the lives of people with cancer. Mnemo is headquartered in Paris with an office in New York City, and it maintains state of the art laboratories in Paris, New York, and Princeton, New Jersey. The company leverages an international talent pool and global resources in its quest to create immunological cures.