Kirsten rat sarcoma virus oncogene homolog G12R mutant peptide epitope (KRAS G12R epitope)

The Mutant KRAS G12R peptide epitope is a tumor-specific neoantigen derived from the Kirsten rat sarcoma virus oncogene homolog (KRAS) protein, featuring a glycine-to-arginine substitution at codon 12 (Waters et al., 2018, Cold Spring Harb Perspect Med). KRAS is a small GTPase that functions as a molecular switch in the RAS/MAPK signaling pathway, and the G12R mutation specifically impairs GTP hydrolysis, leading to constitutive activation and uncontrolled cell growth. This mutant peptide is processed intracellularly and presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, such as HLA-A*11:01, making it a highly specific target for the adaptive immune system (Wang et al., 2016, Cancer Immunol Res). Therapeutic strategies targeting this epitope include TCR-engineered T-cell (TCR-T) therapies and peptide-based vaccines, such as ELI-002, which aim to induce a cytotoxic T-lymphocyte response against malignant cells (Pant et al., 2024, Nature Medicine). Because the G12R epitope is absent in healthy tissues, it offers a high therapeutic index for precision oncology, particularly in pancreatic ductal adenocarcinoma where the mutation is highly prevalent.

Other names

KRAS G12R neoantigenG12R mutant KRAS peptideKRAS G12R-derived epitopeMutant Kirsten rat sarcoma virus oncogene homolog G12R peptide

T-cell receptor (TCR) mediated recognition of the mutant peptide-MHC complex, triggering an adaptive immune response and direct lysis of tumor cells.