Tumor oncogene-derived peptide–HLA class I complex (pHLA-I complex)

Tumor oncogene-derived peptide–HLA class I complexes are molecular assemblies found on the surface of cancer cells, consisting of a short peptide fragment derived from a mutated or overexpressed oncogene bound to a Human Leukocyte Antigen (HLA) class I molecule. These complexes serve as the primary signal for the adaptive immune system to identify and eliminate malignant cells by presenting intracellular protein sequences to CD8+ cytotoxic T cells (Source: NIH National Cancer Institute). Because these peptides often arise from driver mutations (e.g., KRAS, TP53) that are absent in healthy tissue, they represent highly specific targets for immunotherapy, including TCR-engineered T cells and TCR-like antibodies. Therapeutic strategies aim to bypass natural immune tolerance or evasion by engineering high-affinity binders that recognize the unique spatial configuration of the peptide nestled within the HLA groove. However, the effectiveness of targeting these complexes is highly dependent on the patient's specific HLA haplotype and the consistent expression of the MHC machinery by the tumor (Source: Frontiers in Immunology, 2022).

Other names

Peptide-MHC class I complexNeoantigen-HLA complexTumor-specific antigen-HLA complexOncogene-derived neoepitope-HLA complexMHC-peptide complex

Drugs targeting these complexes typically function as T-cell receptor (TCR) mimics or TCR-engineered T-cells (TCR-T) that specifically recognize the peptide-HLA interface to induce cytotoxic T-lymphocyte (CTL) mediated lysis of the tumor cell (Source: Nature Reviews Drug Discovery, 2021).