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, November 7, 2023 – 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. https://doi.org/10.1158/2159-8290.CD-22-1350
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 https://mnemo-tx.com and follow Mnemo Therapeutics on X (@MnemoTx) and LinkedIn.
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