Kirsten rat sarcoma virus oncogene homolog G12V (8–16) peptide presented by Human Leukocyte Antigen A*11:01 (KRAS G12V (8–16)/HLA-A*11:01)

The KRAS G12V (8–16) peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex that serves as a critical target for precision cancer immunotherapy. KRAS is a small GTPase that acts as a molecular switch for signaling pathways controlling cell proliferation and survival; the G12V mutation (Glycine to Valine at position 12) results in a constitutively active protein that drives oncogenesis in various malignancies, including pancreatic, colorectal, and lung adenocarcinomas (Prior et al., 2020, Cancer Research). In patients carrying the HLA-A*11:01 allele—which is highly prevalent in East Asian populations—the mutated KRAS protein is intracellularly processed into a 9-amino acid peptide (VVVGAVGVG) and presented on the cell surface within the MHC Class I groove (Wang et al., 2016, Cancer Immunology Research). This specific peptide-MHC complex is absent in healthy tissues, providing a narrow therapeutic window for immune-based interventions. Current therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines like ELI-002, which are designed to stimulate a robust cytotoxic T-lymphocyte response against cells displaying this mutation (Elicio Therapeutics, 2024). The clinical success of these treatments is strictly dependent on the patient's dual status for the KRAS G12V mutation and the matching HLA-A*11:01 genotype.

Other names

KRAS G12V neoantigenHLA-A*11:01-restricted KRAS G12V peptideVVVGAVGVG-HLA-A*11:01 complexKRAS G12V 8–16/HLA-A*11:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis.