Kirsten rat sarcoma virus oncogene homolog G12V peptide epitope (KRAS G12V peptide)

The Mutant KRAS G12V peptide epitope is a tumor-specific neoantigen derived from the Kirsten rat sarcoma virus oncogene homolog (KRAS) protein, characterized by a glycine-to-valine substitution at the 12th amino acid position (G12V) (MedChemExpress; Frontiers in Immunology). This mutation is a prevalent driver in several aggressive cancers, including pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer (UCLA Health; ESMO). Within tumor cells, the mutant KRAS protein is degraded by the proteasome into short peptides, which are then transported to the cell surface and presented by specific Human Leukocyte Antigen (HLA) class I molecules, such as HLA-A*11:01 or HLA-A*03:01 (NIH; Nature Communications). This peptide-MHC complex acts as a unique target for the immune system, allowing for the development of highly specific immunotherapies (Journal of Clinical Investigation). Current therapeutic strategies include cancer vaccines like ELI-002, which stimulate endogenous T-cell responses, and adoptive cell therapies such as TCR-engineered T cells (TCR-T) that directly target the epitope (Nature Medicine; ESMO). By targeting a neoantigen absent in normal tissues, these approaches aim to maximize anti-tumor efficacy while minimizing off-target toxicity (Cancer Cell; Myrio Therapeutics).

Other names

KRAS G12V neoantigenmKRAS G12V epitopeKRAS G12V mutant peptideKRAS G12V pMHC complexMutant KRAS G12V antigen

T-cell receptor (TCR) recognition of peptide-MHC complexes, induction of T-cell mediated cytotoxicity, and stimulation of antigen-specific immune responses.