HLA-A*11:01-restricted KRAS G12V peptide-major histocompatibility complex (HLA-A*11:01/KRAS G12V pMHC)

The HLA-A*11:01–KRAS G12V peptide-MHC complex is a specific molecular target consisting of a mutated KRAS peptide (G12V) presented by the Human Leukocyte Antigen (HLA) allele A*11:01. KRAS is a GTPase that plays a critical role in cell signaling, and the G12V mutation is a common oncogenic driver in various cancers, including pancreatic, colorectal, and lung adenocarcinomas (PubMed: 35648703). This complex serves as a neoantigen, a tumor-specific marker that can be recognized by the immune system, specifically by T-cell receptors (TCRs). Because the G12V mutation is absent in healthy tissues, this pMHC complex is an ideal target for highly specific immunotherapies such as TCR-engineered T-cell (TCR-T) therapy and cancer vaccines (PubMed: 26934341). Therapeutic strategies involve developing synthetic TCRs or bispecific molecules that bind with high affinity to this specific peptide-HLA combination to trigger a cytotoxic immune response against tumor cells. Clinical development focuses on patients who are both HLA-A*11:01 positive and harbor the KRAS G12V mutation, representing a precision medicine approach to oncology.

Other names

KRAS G12V/HLA-A*11:01 complexHLA-A*11:01-presented KRAS G12V neoantigenKRAS G12V-HLA-A1101HLA-A*11:01-restricted KRAS G12V

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis.