Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V 9-mer peptide presented by HLA-A*11:01 (KRAS G12V/HLA-A*11:01)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V 9-mer peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex that serves as a critical target for precision immunotherapy. This complex is formed when the mutated KRAS protein, featuring a glycine-to-valine substitution at codon 12, is intracellularly processed into a 9-amino acid fragment (typically residues 7-15, VVVGAVGVG) and displayed on the cell surface by the Human Leukocyte Antigen (HLA) allele A*11:01 (PubMed: 26437906). KRAS is a GTPase that normally regulates cell signaling; however, the G12V mutation results in constitutive activation, driving oncogenesis in pancreatic, colorectal, and lung cancers (PubMed: 31844256). Because this specific peptide-MHC (pMHC) complex is absent in healthy tissues, it allows for the development of highly selective therapies such as T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific antibodies. One notable candidate in development is AFNT-211, a TCR-T therapy designed to recognize this specific epitope. The HLA-A*11:01 allele is particularly common in East Asian populations, making this target a significant focus for addressing cancer in these demographics. Effective targeting requires rigorous patient screening for both the KRAS G12V mutation and the HLA-A*11:01 genotype to ensure therapeutic efficacy and minimize off-target risks.

Other names

KRAS G12V neoantigenHLA-A*11:01-restricted KRAS G12V peptideKRAS G12V (7-15) HLA-A*11:01 complexpMHC KRAS G12V/HLA-A*11:01KRAS G12V (VVVGAVGVG) HLA-A*11:01 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the tumor cell surface, leading to the activation of cytotoxic T-lymphocytes and subsequent granzyme/perforin-mediated apoptosis of the target cell.