Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8⁺ T cell adoptive therapies in pre-clinical studies.

ABSTRACT: Mitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies. We demonstrate that MCJ inhibits mitochondrial respiration in murine CD8⁺ CAR-T cells and that deletion of MCJ increases their in vitro and in vivo efficacy against murine B cell leukaemia. Similarly, MCJ deletion in ovalbumin (OVA)-specific CD8⁺ T cells also increases their efficacy against established OVA-expressing melanoma tum

SUBMITTER: Wu MH 

PROVIDER: S-EPMC11126743 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature