Mutant Kirsten rat sarcoma viral oncogene homolog G12C peptide epitope (KRAS G12C epitope)

The Mutant KRAS G12C peptide epitope is a tumor-specific neoantigen generated by a missense mutation in the KRAS oncogene, where glycine is substituted by cysteine at codon 12 [1]. This mutation is a primary driver in several aggressive malignancies, including non-small cell lung cancer (NSCLC), colorectal cancer, and pancreatic ductal adenocarcinoma [3]. In the context of immunotherapy, the mutant KRAS protein is processed intracellularly into short peptide fragments that are subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) molecules [4]. These peptide-MHC complexes are recognized as foreign by the immune system, specifically by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, making them ideal targets for precision immunotherapy [1, 2]. Therapeutic strategies leveraging this epitope include cancer vaccines, such as mRNA-5671 and ELI-002, as well as adoptive cell therapies using TCR-engineered T-cells [1, 2]. Unlike small-molecule inhibitors that bind to the protein's switch II pocket, epitope-targeted therapies aim to induce a systemic, long-lasting immune response against cells harboring the mutation [3]. However, the efficacy of these treatments is often dependent on the patient's specific Human Leukocyte Antigen (HLA) type, which determines whether the epitope can be successfully presented to T-cells [2, 4].

Other names

KRAS G12C neoantigenKRAS G12C mutant peptideKRAS G12C-derived peptideKRAS G12C pMHC complexKirsten rat sarcoma G12C epitope

Induction of a targeted adaptive immune response through the activation of CD8+ and CD4+ T-cells that specifically recognize the mutant G12C peptide presented on MHC molecules, leading to the selective lysis of tumor cells [1, 3].