HLA-A*11:01–KRAS G12V mutant peptide complex (HLA-A*11:01/KRAS-G12V)

The HLA-A*11:01–KRAS G12V mutant peptide complex is a highly specific tumor neoantigen formed by the presentation of a mutated KRAS peptide on the surface of cancer cells via the Major Histocompatibility Complex (MHC) Class I allele HLA-A*11:01. The KRAS G12V mutation involves a glycine-to-valine substitution at codon 12, which locks the KRAS protein in a constitutively active state, driving uncontrolled cell proliferation in cancers such as pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer (PubMed: 31578134). This specific peptide-MHC (pMHC) complex serves as a critical recognition element for the cellular immune system, particularly cytotoxic T lymphocytes (CTLs). Therapeutic interventions targeting this complex include TCR-engineered T-cell (TCR-T) therapies and peptide-based vaccines designed to elicit a robust and specific immune response against tumor cells harboring the mutation (PubMed: 27199428). Because the G12V mutation is somatic and tumor-specific, the complex is an ideal target for precision immunotherapy with a low risk of on-target, off-tumor toxicity. However, challenges remain, such as the potential for tumor immune evasion through HLA downregulation or the loss of the mutant allele. Clinical development is currently focused on identifying high-affinity T-cell receptors and optimizing delivery platforms to overcome the immunosuppressive tumor microenvironment.

Other names

HLA-A*11:01/KRAS-G12VKRAS G12V neoantigenHLA-A11-restricted KRAS G12V peptideHLA-A*11:01-KRAS(G12V) complexHLA-A*11:01-restricted KRAS G12V mutant peptide complex

The primary mechanism of action involves the specific recognition of the HLA-A*11:01–KRAS G12V complex by the T-cell receptor (TCR) of engineered or endogenous T cells, leading to the formation of an immunological synapse, secretion of cytotoxic granules (perforin and granzymes), and subsequent apoptosis of the target tumor cell (PubMed: 27199428).