Autophagy disruption primes CAR-T cell metabolism for sustained rejection of ovarian tumors.

ABSTRACT: T-cell based immunotherapies such as chimeric antigen receptor T (CAR-T) cell therapy face substantial hurdles when confronting solid tumors such as ovarian cancer, where metabolic constraints in the tumor microenvironment limit T cell infiltration and function. In particular, T cells exposed to nutrient deprivation and hypoxia upregulate autophagy, a lysosomal degradation pathway that negatively regulates effector responses. Here, we used CRISPR-Cas9 to target a folate receptor alpha (αFR) CAR expression cassette into the locus of the essential autophagy gene ATG5, thereby generating autophagy-deficient CAR-T cells in a single editing step. Targeted metabolite profiling revealed that deletion of ATG5 induced widespread metabolic reprogramming characterized by increased gluco

SUBMITTER: Carleton GA 

PROVIDER: S-EPMC12632499 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature