TET2 guards against unchecked BATF3-induced CAR T cell expansion.

ABSTRACT: Further advances in cell engineering are needed to increase the efficacy of chimeric antigen receptor (CAR) and other T cell-based therapies^1-5. As T cell differentiation and functional states are associated with distinct epigenetic profiles^6,7, we hypothesized that epigenetic programming may provide a means to improve CAR T cell performance. Targeting the gene that encodes the epigenetic regulator ten-eleven translocation 2 (TET2)⁸ presents an interesting opportunity as its loss may enhance T cell memory^9,10, albeit not cause malignancy^9,11,12. Here we show that disruption of TET2 enhances T cell-mediated tumour rejection in leukaemia and prostate cancer models. However, loss of TET2 also enables antigen-independent CAR T cell clonal

SUBMITTER: Jain N 

PROVIDER: S-EPMC10511001 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature