Tumor-associated peptide-HLA class I complex (pHLA-I) (pHLA-I)

Tumor-associated peptide-HLA class I complexes are molecular assemblies on the surface of cancer cells that present intracellular protein fragments to the immune system (Source: Nature Reviews Cancer, PMID: 33859381). These complexes consist of a tumor-derived peptide, typically 8-11 amino acids long, non-covalently bound to a Human Leukocyte Antigen (HLA) class I molecule and beta-2 microglobulin (Source: UniProt, P04439). Recognition of these complexes by the T-cell receptor (TCR) on CD8+ T cells is the fundamental mechanism for immunosurveillance and the elimination of malignant cells. Modern immunotherapies, including TCR-engineered T cells (TCR-T) and bispecific T-cell engagers like ImmTACs, are designed to specifically bind these pHLA targets to trigger potent anti-tumor responses (Source: NEJM, PMID: 34551227). Because HLA molecules are highly polymorphic, these treatments are usually restricted to patients carrying specific alleles, most commonly HLA-A*02:01. Therapeutic challenges include the risk of off-target toxicity due to cross-reactivity with similar peptides in healthy tissues and the potential for tumor escape through HLA downregulation (Source: Journal for ImmunoTherapy of Cancer, PMID: 32606053).

Other names

pMHC-I complexPeptide-MHC class I complexTumor antigen-HLA complexHLA-restricted tumor antigenTumor-associated antigen-HLA complexpHLA complex

Therapeutic agents such as TCR-engineered T cells or bispecific TCR molecules bind specifically to the peptide-HLA complex on the tumor cell surface, facilitating T-cell mediated lysis of the target cell (Source: Nature Reviews Cancer, PMID: 33859381).