Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.

ABSTRACT: High levels of asparagine synthetase (ASNS) in acute lymphoblastic leukemia (ALL) lead to immunotherapy resistance. Our study showed that ASNS overexpression (OE) in NALM6-GL cancer cells attenuated chimeric antigen receptor (CAR)-T cell-mediated cancer cell lysis. Asparaginase (ASPG) is an approved drug that breaks down circulating asparagine in leukemia cells, thereby depriving cancer cells of asparagine and inhibiting cancer growth. We proposed a hypothesis that ASPG-engineered CAR-T cells undergo phenotype switching to overcome immunotherapy resistance in ALL. Coculture killing assay showed ASPG-OE CAR-T cells exhibited increased killing efficacy against ASNS-OE cancer cells by enhancing the expression of granzyme B, interferon gamma, and tumor necrosis factor alpha, whereas ASPG-knock

SUBMITTER: Zhu X 

PROVIDER: S-EPMC12628164 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature