KRAS G12V mutant peptide–HLA-A*03:01 complex (KRAS G12V-HLA-A*03 complex)

The KRAS G12V mutant peptide–HLA-A*03:01 complex is a tumor-specific antigenic complex generated when the KRAS gene, mutated at codon 12 from glycine (G) to valine (V), is processed in tumor cells and loaded onto the HLA-A*03:01 class I major histocompatibility complex (MHC) molecule. This neoantigen is not present in healthy tissue and is recognized specifically by certain cytotoxic T lymphocyte (CTL) receptors (TCRs), making it a highly attractive target for immunotherapy, particularly TCR-engineered cell therapies. The precise recognition arises from the altered peptide sequence (e.g., VVVGAVGVGK), and only TCRs highly specific for this peptide-MHC combination are activated, thereby potentially sparing normal cells. Mutant KRAS G12V is highly prevalent in cancers such as pancreatic, colorectal, and lung adenocarcinomas. The therapeutic targeting of this complex is being advanced mainly via adoptive T cell transfer of TCRs engineered for exquisite specificity for the KRAS G12V–HLA-A*03:01 neoepitope. Key development challenges include ensuring tumor selectivity, preventing off-target toxicities, and overcoming tumor immune evasion mechanisms such as antigen loss or HLA downregulation [1][3][9].

Other names

KRAS G12V neoantigen–HLA-A*03:01KRAS G12V/HLA-A*03:01mutant KRAS G12V presented by HLA-A*03KRAS G12V/A3

Recognition and killing of tumor cells by TCR-engineered T cells specific for KRAS G12V–HLA-A*03:01 neoepitope Potentially by other forms of adoptive cell therapy (ACT)