Human leukocyte antigen A*11:01-restricted Kirsten rat sarcoma virus oncogene homolog G12V peptide-major histocompatibility complex (HLA-A*11:01/KRAS G12V pMHC)

The HLA-A*11:01–KRAS G12V peptide–MHC complex is a tumor-specific neoantigen target used in advanced cancer immunotherapy. It consists of a 9- or 10-amino acid peptide derived from the mutated KRAS protein (where glycine at position 12 is replaced by valine) presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*11:01 (Source: PubMed PMID: 26479923). KRAS mutations are among the most frequent drivers of human cancers, particularly in pancreatic, colorectal, and lung adenocarcinomas, and the G12V variant is a highly prevalent isoform (Source: COSMIC database). This complex is absent on normal tissues, making it an ideal target for T-cell receptor (TCR) engineered therapies that aim to achieve high specificity and minimal off-target effects (Source: Nature Communications, 2021). Drugs targeting this complex, such as KITE-712 and AFNT-211, utilize engineered T-cells to recognize the specific peptide-HLA interface, triggering a potent cytotoxic immune response against the tumor (Source: Kite Pharma/Gilead Sciences; Affini-T Therapeutics). Clinical application requires patient screening for both the specific HLA-A*11:01 genotype and the presence of the KRAS G12V mutation to ensure therapeutic efficacy. The recognition of this complex by a TCR leads to the formation of an immunological synapse and subsequent release of perforins and granzymes to induce apoptosis in the target cell. Therapeutic challenges include potential immune escape through HLA downregulation or antigen loss, as well as the management of cytokine release syndrome (Source: Journal of Hematology & Oncology, 2023).

Other names

KRAS G12V neoantigenHLA-A*11:01/KRAS G12V complexKRAS G12V-HLA-A*11:01KRAS G12V-specific pMHC

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