Kirsten rat sarcoma virus oncogene homolog G12C mutant peptide antigen (KRAS G12C peptide)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12C mutant peptide antigen is a tumor-specific neoantigen derived from the KRAS protein carrying a glycine-to-cysteine substitution at position 12 [NIH, PubMed]. This mutation is a frequent oncogenic driver in various malignancies, particularly non-small cell lung cancer, colorectal cancer, and pancreatic ductal adenocarcinoma [NCI, NIH]. In cancer cells, the mutant protein is processed by the proteasome into short peptide fragments, which are then presented on the cell surface by Major Histocompatibility Complex (MHC) molecules [NIH, Elicio Therapeutics]. These peptide-MHC complexes serve as unique targets for the immune system, as they are absent in normal tissues [NCI, PubMed]. Therapeutic strategies targeting this antigen include cancer vaccines, such as mRNA or peptide-based formulations, and adoptive T-cell therapies (TCR-T), which aim to prime or engineer T cells to recognize and eliminate cells displaying the G12C neoepitope [Moderna, Elicio Therapeutics]. While small-molecule inhibitors like sotorasib directly target the KRAS G12C protein, the peptide antigen approach offers a complementary immunotherapy route to overcome resistance and provide durable anti-tumor immunity [NIH, Cancer.gov].

Other names

KRAS G12C neoantigenKRAS G12C mutant peptidemKRAS G12C peptideKRAS G12C neoepitopeKRAS G12C mutant epitope

Induces or directs a T-cell mediated immune response (CD4+ and CD8+) against tumor cells that present the KRAS G12C mutant peptide on their surface via MHC Class I or II molecules.