Kirsten rat sarcoma virus oncogene homolog-derived peptide presented by Human Leukocyte Antigen class I (KRAS-peptide-HLA-I complex)

The KRAS-derived peptide presented by HLA class I is a critical neoantigen target in oncology, representing a complex formed when mutated KRAS proteins are processed into short peptides and displayed on the cell surface by Human Leukocyte Antigen (HLA) molecules. KRAS is a GTPase that normally regulates cell signaling pathways like MAPK and PI3K; however, mutations at codons 12, 13, or 61 lead to constitutive activation and drive the progression of various aggressive malignancies, including pancreatic, colorectal, and lung cancers (PubMed: 33009416). Because these mutant peptides are unique to tumor cells, they serve as highly specific targets for the immune system, particularly CD8+ cytotoxic T-cells. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, which utilize synthetic receptors designed to recognize specific peptide-HLA combinations, and cancer vaccines (such as ELI-002) that aim to expand endogenous T-cell populations against these neoantigens (Nature: 10.1038/s41586-023-06963-6). Unlike small-molecule KRAS inhibitors that bind directly to the protein's pocket, these immunotherapies rely on the intracellular processing and surface presentation of the mutant protein. The efficacy of these treatments is highly dependent on the patient's specific HLA allele and the presence of the corresponding KRAS mutation, making patient stratification essential for clinical success (NEJM: 375:2255-2262).

Other names

KRAS neoantigen-HLA complexKRAS mutant peptide-MHC class I complexKRAS-pHLAKRAS-MHC-IMutant KRAS-HLA-A*11:01 complexMutant KRAS-HLA-C*08:02 complex

T-cell receptor (TCR) mediated recognition, T-cell activation, Cytotoxic T-lymphocyte (CTL) mediated cell lysis, Vaccine-induced immune priming