KRAS G12V mutant peptide presented by HLA-A*03:01 (KRAS G12V/HLA-A*03:01)

The KRAS G12V mutant peptide presented by HLA-A*03:01 is a tumor-specific neoantigen complex that serves as a critical target for precision immunotherapy (PubMed: 30617141). KRAS is a member of the RAS family of small GTPases that regulate cell signaling pathways involved in growth and survival; the G12V mutation results in constitutive activation, driving oncogenesis in various malignancies including pancreatic, colorectal, and lung cancers (PubMed: 31515431). In patients carrying the HLA-A*03:01 allele, the mutated KRAS protein is processed into short peptides containing the G12V substitution, which are then displayed on the cell surface by the Major Histocompatibility Complex (MHC) Class I molecule. This specific peptide-MHC complex can be recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, making it an ideal target for TCR-engineered T-cell (TCR-T) therapies and cancer vaccines (PubMed: 27251264). Because the G12V mutation is absent in healthy tissues, targeting this complex offers high specificity, potentially minimizing off-target effects. Current therapeutic strategies focus on developing high-affinity TCRs that can selectively bind this complex to induce a potent anti-tumor immune response (NCT03745326).

Other names

KRAS G12V/HLA-A*03:01 complexHLA-A*03:01-restricted KRAS G12V neoantigenKRAS G12V-A3 complexVVVGAVGVG/HLA-A*03:01

Binding of engineered T-cell receptors (TCRs) to the peptide-MHC complex, triggering cytotoxic T-lymphocyte activation and tumor cell lysis.