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

The KRAS G12V neoantigen peptide presented by HLA-A*11:01 is a specific peptide-MHC (pMHC) complex that serves as a critical target for precision cancer immunotherapy. KRAS is a small GTPase that regulates cell signaling; the G12V mutation (glycine to valine at position 12) is a common oncogenic driver that leads to uncontrolled cell proliferation in pancreatic, colorectal, and lung cancers (PubMed: 30447037). In patients carrying the HLA-A*11:01 allele, the mutated KRAS protein is processed into a 9-mer peptide (VVVGAVGVG) and presented on the cell surface by the MHC Class I molecule (PubMed: 26479480). This complex is recognized as "non-self" by the immune system, allowing for the development of highly specific therapies such as TCR-engineered T cells (TCR-T) and neoantigen vaccines (PubMed: 34010245). Because the G12V mutation is tumor-specific, targeting this complex minimizes damage to healthy tissues. Current clinical efforts, including mRNA-based vaccines and adoptive cell therapies, aim to harness this specificity to treat advanced solid tumors in HLA-matched patients (ClinicalTrials.gov: NCT03948191).

Other names

KRAS G12V-HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12V peptideKRAS G12V pMHC

The mechanism involves the specific recognition of the KRAS G12V peptide/HLA-A*11:01 complex by engineered or endogenous T-cell receptors (TCRs), which triggers the activation of CD8+ T cells and subsequent granzyme/perforin-mediated apoptosis of the target tumor cells (PubMed: 34010245).