KRAS G12V 9-mer neoantigen peptide presented by HLA-A*11:01 (KRAS G12V/HLA-A*11:01)

The KRAS G12V 9-mer neoantigen peptide presented by HLA-A*11:01 is a specific peptide-major histocompatibility complex (pMHC) found on the surface of cancer cells harboring the KRAS G12V mutation (PubMed: 27932491). KRAS is a GTPase that acts as a molecular switch in signal transduction; the G12V mutation results in a constitutively active protein that drives uncontrolled cell proliferation and survival in various cancers (NIH: National Cancer Institute). This specific 9-mer peptide (typically VVVGAVGVG) is a product of intracellular processing of the mutant KRAS protein and is presented by the HLA-A*11:01 molecule, a common MHC Class I allele in certain populations (PubMed: 31515456). Because this neoantigen is derived from a somatic mutation, it is not present in healthy tissues, making it an ideal target for precision immunotherapies such as TCR-engineered T-cells (TCR-T) and personalized cancer vaccines. Therapeutic interventions aim to leverage the specificity of the T-cell receptor to recognize this pMHC, thereby inducing a potent and selective immune response against tumor cells. Clinical application requires patient screening for both the specific KRAS G12V mutation and the HLA-A*11:01 genotype to ensure target availability.

Other names

KRAS G12V neoantigen-HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12V peptideKRAS G12V 9-mer/HLA-A*11:01VVVGAVGVG/HLA-A*11:01 complex

The target is recognized by engineered T-cell receptors (TCRs) that specifically bind the peptide-MHC complex, triggering T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and subsequent apoptosis of the tumor cell (PubMed: 27932491).