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Releasing the mitochondrial respiration brake MCJ/DnaJC15 enhances CD8 CAR-T cell therapy efficacy

GSE263259 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/05/02 Platform GPL24247
Summary
Metabolism of chimeric antigen receptor (CAR) T cells is emerging as an important area to improve CAR-T cell therapy in cancer treatment. Mitochondrial respiration is essential for survival and function of CAR-T cells, but developing strategies to specifically enhance mitochondrial respiration has been challenging. Here we identify MCJ/DnaJC15, an endogenous negative regulator of mitochondrial Complex I, as a metabolic target to enhance mitochondrial respiration in CD8 CAR-T cells. Loss of MCJ in CD8 CAR-T cells increases their in vitro and in vivo efficacy against mouse B cell leukemias. MCJ deficiency in TCR- specific CD8 cells also increases their efficacy against solid tumors in vivo. Furthermore, we reveal that human CD8 cells express MCJ and that silencing MCJ expression increases mitochondrial metabolism and anti-tumor activity of human CAR-T cells. Thus, we demonstrate the unique therapeutic potential of targeting MCJ to enhance the metabolism and efficacy of adoptive T cell therapies.
Published in
Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8(+) T cell adoptive therapies in pre-clinical studies
Wu MH, Valenca-Pereira F, Cendali F et al. · Nature communications 2024 · PMID 38789421 · doi:10.1038/s41467-024-48653-y
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Also filed as BioProject PRJNA1096360 and SRA study SRP499833. Searching any of these in the dataset finder brings you back here.

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