KRAS G12V mutant peptide presented by Human Leukocyte Antigen A*11:01 (HLA-A*11:01) (KRAS G12V/HLA-A*11:01)

The KRAS G12V mutant peptide presented by Human Leukocyte Antigen A*11:01 (HLA-A*11:01) is a tumor-specific neoantigen complex that serves as a high-priority target for cancer immunotherapy. KRAS is a member of the RAS GTPase family that regulates cell growth and survival; mutations at codon 12, specifically the G12V substitution (Glycine to Valine), result in a constitutively active protein that drives oncogenesis in approximately 30% of pancreatic cancers and 10% of colorectal cancers [PubMed: 31843910]. Intracellular processing of the mutant KRAS protein generates neoantigenic peptides that are presented on the cell surface by the HLA-A*11:01 allele, which is particularly prevalent in East Asian populations [PubMed: 34407445]. This peptide-MHC complex is absent on healthy cells, providing a narrow therapeutic window for targeted therapies such as TCR-engineered T-cells (TCR-T) and bispecific antibodies. Drugs like AFNT-211 are designed to specifically recognize this complex, triggering a potent T-cell mediated cytotoxic response against the tumor [Affini-T Therapeutics]. Clinical success depends on the precise identification of patients harboring both the specific KRAS mutation and the HLA-A*11:01 genotype.

Other names

KRAS G12V-HLA-A*11:01 complexKRAS G12V neoantigenHLA-A*11:01-restricted KRAS G12VKRAS G12V pMHC

Binding of engineered T-cell receptors (TCRs) or TCR-like antibodies to the peptide-MHC complex, leading to T-cell activation and targeted lysis of tumor cells expressing the KRAS G12V mutation [PubMed: 34407445].