A novel mitochondrial pyruvate carrier inhibitor drives stem cell-like memory CAR T cell generation and enhances antitumor efficacy.

ABSTRACT: Adoptive cell transfer with chimeric antigen receptor (CAR)-expressing T cells can induce remarkable complete responses in cancer patients. Therapeutic success has been correlated with central and stem cell-like memory T cell subsets in the infusion product, which are better able to drive efficient CAR T cell in vivo expansion and long-term persistence. We previously reported that inhibition of the mitochondrial pyruvate carrier (MPC) during mouse CAR T cell culture induces a memory phenotype and enhances antitumor efficacy against melanoma. Here, we use a novel MPC inhibitor, MITO-66, which robustly induces a stem cell-like memory phenotype in CD19-CAR T cells generated from healthy donors and patients with relapsed/refractory B cell malignancies. MITO-66-conditioned CAR T cells we

SUBMITTER: Wenes M 

PROVIDER: S-EPMC11570499 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature