KRAS G12V 8–16 neoepitope presented by HLA-A*11:01 (KRAS G12V/HLA-A*11:01)

The KRAS G12V 8–16 neoepitope presented by HLA-A*11:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a therapeutic target for cancer immunotherapy. KRAS is a small GTPase that regulates cell signaling; mutations such as the glycine-to-valine substitution at codon 12 (G12V) lead to constitutive activation and drive the progression of various cancers, including pancreatic, colorectal, and lung adenocarcinoma (PMID: 30475650). The 8–16 neoepitope refers to a 9-amino acid peptide fragment (VVGAVGVGK) derived from the mutated KRAS protein, which is processed and presented on the cell surface by the HLA-A*11:01 allele (PMID: 26844605). This pMHC complex is recognized by specific T-cell receptors (TCRs), allowing for the development of TCR-engineered T-cell (TCR-T) therapies that can selectively eliminate tumor cells while sparing healthy tissue. Because the G12V mutation is a neoantigen not found in normal cells, it represents a highly specific target for precision oncology. Clinical strategies targeting this complex involve identifying patients who are both HLA-A*11:01 positive and harbor the KRAS G12V mutation, followed by treatment with TCR-T cells designed to bind the pMHC and induce a cytotoxic immune response (PMID: 27929005).

Other names

KRAS G12V (8-16) peptide-HLA-A*11:01 complexVVGAVGVGK/HLA-A*11:01KRAS G12V neoantigen

T-cell receptor (TCR) recognition of the peptide-MHC complex on the tumor cell surface, leading to T-cell activation, secretion of cytotoxic granules (perforin/granzymes), and induction of apoptosis in the target cell.