KRAS G12V peptide–HLA-A*03 complex (KRAS G12V/HLA-A*03)

The KRAS G12V peptide–HLA-A*03 complex is a tumor-specific neoantigen consisting of a mutated fragment of the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein bound to the Human Leukocyte Antigen (HLA) A*03:01 molecule (Wang et al., 2016). KRAS is a small GTPase that regulates signaling pathways for cell growth; the G12V mutation results in a constitutively active protein that drives uncontrolled proliferation in pancreatic, colorectal, and lung cancers (Prior et al., 2020). This complex is presented on the surface of malignant cells, making them visible to the adaptive immune system, specifically CD8+ cytotoxic T-lymphocytes. Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies and neoantigen vaccines like ELI-002, which aim to induce a robust immune response against the mutation while sparing healthy cells (Pant et al., 2024). Because the G12V mutation is absent in normal tissue, the complex provides a high degree of therapeutic selectivity. However, challenges such as HLA downregulation and the immunosuppressive tumor microenvironment can limit treatment efficacy. Patient selection for these therapies requires screening for both the specific KRAS mutation and the HLA-A*03 genotype.

Other names

KRAS G12V/HLA-A*03:01 complexHLA-A*03:01-presented KRAS G12V peptideKRAS G12V neoantigen-MHC complexKRAS G12V-A03 complex

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