Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity
Menée in vitro et à l'aide de xénogreffes sur un modèle murin, cette étude met en évidence un mécanisme par lequel la délétion de la méthyltransférase DNMT3A dans les lymphocytes CAR-T prévient leur dysfonctionnement et augmente leur activité antitumorale
Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer treatment. However, a major limitation of CAR T cell therapies is the development of exhaustion during extended antigen exposure. Here, Prinzing et al. showed that epigenetic changes in CAR T cells, modulated by DNA methyltransferase 3 alpha (DNMT3A), drive exhaustion. Deletion of DNMT3A from CAR T cells prevented dysfunction and enhanced antitumor activity of CAR T cells in an interleukin-10–dependent manner. These results show that targeting epigenetic programs in CAR T cells may further improve their efficacy.