AACR 2024: Targeting mutant KRAS proteins with novel TCR-mimic fully human antibodies
Used in the poster: TCR-Mimic Antibody Platform
Summary:
Novel antibodies highly specific to KRAS mutations (G12V and G12D) presented by human leukocyte antigen (HLA) were discovered using proprietary RenTCR-mimicTM mice and high-throughput Beacon-based screening. These TCR-mimic antibodies exhibit higher affinities than endogenous TCRs and demonstrate diverse epitope targeting. Despite the low KRAS mutant peptide-HLA complex density on pancreatic cancer cell surfaces, the antibodies showed potent in vitro tumor lysis activity when assembled into CD3 T cell engagers, with a convincing lack of off-target binding. These findings suggest promising therapeutic potential for targeting KRAS mutations in solid tumors.
