Targeting mutated KRAS by HLA-A*02:01 restricted anti-KRAS TCR-mimic CAR and bispecific T cell engager.

ABSTRACT: Mutations in the KRAS proto-oncogene, particularly at codon 12, are among the most frequent genetic alterations in various cancers, and KRAS^G12V accounts for about 25% of all KRAS mutations observed in lung, pancreatic, and colorectal adenocarcinomas. Despite improved treatment regimes using targeted therapy and checkpoint inhibitors, cellular immunotherapy options for KRAS-mutated cancers remain elusive. We therefore developed two TCR-mimic (TCRm) anti-KRAS^G12V/HLA-A*02:01 chimeric antigen receptors (CARs) containing different hinge regions and, alternatively, a TCRm anti-KRAS^G12V/HLA-A*02:01 bispecific T cell engager (BiTE) to explore immunotherapy to the highly prevalent KRAS^G12V neoantigen. CAR-redirected or BiTE-exposed JNL-reporter cells de

SUBMITTER: Ebrahimi S 

PROVIDER: S-EPMC12449438 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature