Alpha-fetoprotein peptide-HLA complex (AFP-HLA)

Alpha-fetoprotein (AFP) is a glycoprotein primarily produced during fetal development by the yolk sac and liver, with levels dropping significantly after birth (UniProt P02771). In adults, AFP is frequently overexpressed in hepatocellular carcinoma (HCC) and certain germ cell tumors, making it a classic tumor marker (PubMed: 32433714). While secreted AFP is used for diagnosis, intracellular AFP is processed into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, specifically the HLA-A*02:01 allele (PubMed: 11418444). This AFP peptide-HLA complex serves as a specific target for T-cell-based therapies, as it allows the immune system to recognize intracellular oncogenic proteins that are not accessible to standard monoclonal antibodies (Eureka Therapeutics). Therapeutic approaches include TCR-engineered T-cells (TCR-T) and TCR-mimic (TCRm) antibodies, which bind the complex with high specificity to induce tumor cell lysis (PubMed: 28100703). Clinical candidates like ADP-A2AFP and ET1402L1 have been developed to target this complex in patients with AFP-positive HCC who carry the appropriate HLA genotype (Adaptimmune; ClinicalTrials.gov: NCT03132792).

Other names

AFP-MHC complexAFP158-166/HLA-A*02:01Alpha-fetoprotein-MHC class I complexAFP-HLA-A2

T-cell receptor (TCR) or TCR-like antibody recognition of the intracellularly derived AFP peptide presented on the cell surface by HLA molecules, leading to T-cell mediated lysis of the target cell.