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The KRAS G12V mutant neoantigen peptide presented by HLA-A*11:01 is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. KRAS is a small GTPase that acts as a molecular switch in the RAS/MAPK signaling pathway, regulating cell growth and survival; the G12V mutation (glycine to valine at codon 12) results in constitutive activation of the protein, driving oncogenesis in various malignancies including pancreatic, colorectal, and lung cancers (Source: PubMed, PMID: 30409917). When the mutant KRAS protein is processed by the proteasome, the resulting neoantigenic peptides, such as the 10-mer VVVGAVGVGK, are loaded onto HLA-A*11:01 molecules and displayed on the cell surface for recognition by the immune system (Source: NIH, ClinicalTrials.gov). This specific pMHC complex serves as a highly selective target for T-cell receptor (TCR)-engineered T-cell therapies and neoantigen vaccines, as it is expressed exclusively by tumor cells harboring the mutation and the specific HLA allele (Source: Nature Communications, DOI: 10.1038/s41467-021-24366-9). Therapeutic strategies targeting this complex aim to induce a potent, mutation-specific cytotoxic T-lymphocyte response to eradicate tumor cells while sparing healthy tissue that lacks the somatic mutation.
T-cell receptor (TCR) binding, T-cell mediated cytotoxicity, Immune system stimulation, MHC-restricted antigen recognition
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