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

The KRAS G12V neoepitope peptide presented by HLA-A*11:01 is a tumor-specific antigen complex consisting of a mutated fragment of the KRAS protein (Glycine to Valine at position 12) bound to the Human Leukocyte Antigen (HLA) allele A*11:01. KRAS is a GTPase that normally regulates cell signaling, but the G12V mutation results in constitutive activation, driving the progression of aggressive malignancies such as pancreatic, colorectal, and lung cancers (PubMed: 31843910). This specific peptide-MHC complex is a primary target for immunotherapy because it is uniquely expressed on tumor cells and absent in healthy tissues, providing a high degree of therapeutic specificity. Current drug development focuses on T-cell receptor (TCR) engineered T-cell therapies and neoantigen vaccines designed to prime the immune system to recognize and destroy cells displaying this complex (NEJM 2022; 386:2112-2119). Clinical success depends on the precise matching of the patient's tumor mutation profile and their HLA genotype, as HLA-A*11:01 is particularly prevalent in certain populations, such as those of East Asian descent. Challenges in targeting this complex include potential immune escape through the loss of HLA expression or the development of an immunosuppressive tumor microenvironment.

Other names

KRAS G12V-HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12V neoantigenKRAS G12V peptide-MHC complexG12V neoepitope

Therapeutic agents such as TCR-engineered T cells or vaccines target the specific peptide-MHC complex to induce a cytotoxic T-lymphocyte response against tumor cells expressing the mutated KRAS G12V protein.