KRAS^G12V/HLA-A*02:01-targeted chimeric antigen receptor T cells exhibit potent preclinical activity against solid tumors.

ABSTRACT: Despite advances in chimeric antigen receptor T cell (CAR T cell) therapy for leukemia and lymphoma, solid tumors remain challenging because of limited target specificity and safety concerns. Neoantigens like KRAS^G12V, a highly prevalent yet undruggable mutation in solid tumors, offer tumor-exclusive specificity. This study developed CAR T cells targeting KRAS^G12V/HLA-A*02:01 using phage antibody display to identify high-affinity single-chain variable fragments. Engineered B9 CAR T cells specifically lysed tumor cells and patient-derived cancer organoids expressing KRAS^G12V/HLA-A*02:01, demonstrating potent antitumor activity. Animal studies showed that B9 CAR T cells effectively controlled tumor growth in subcutaneous pancreatic ductal adenocarcinoma (PDAC

SUBMITTER: Shao H 

PROVIDER: S-EPMC12922744 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature