Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V neoantigen presented by Human Leukocyte Antigen (HLA) A*11:01 (KRAS G12V/HLA-A*11:01)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V neoantigen presented by Human Leukocyte Antigen (HLA) A*11:01 is a specific peptide-major histocompatibility complex (pMHC) found on the surface of tumor cells harboring the KRAS G12V mutation. KRAS is a small GTPase that acts as a molecular switch in signaling pathways like MAPK/ERK, and the G12V mutation leads to constitutive activation, driving oncogenesis in pancreatic, colorectal, and lung cancers (PubMed: 31515456). In patients with the HLA-A*11:01 allele, the mutated KRAS protein is processed into peptides, such as the 10-mer VVVGAVGVGK, which are then presented by the HLA molecule to the immune system (PubMed: 26494315). This complex serves as a highly specific target for cancer immunotherapies, including T-cell receptor (TCR) engineered T-cell therapies and neoantigen vaccines (Affini-T Therapeutics). Because the target is a neoantigen resulting from a somatic mutation, it is absent in normal tissues, potentially offering a wide therapeutic window with minimal off-target effects. However, challenges include the heterogeneity of HLA expression and the potential for tumor immune escape through HLA downregulation or loss of heterozygosity (PubMed: 30249674).

Other names

KRAS G12V peptide-HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12V neoantigenKRAS G12V/A11:01KRAS G12V/HLA-A11

T-cell receptor (TCR) binding and subsequent T-cell mediated lysis of tumor cells