Alpha-fetoprotein (AFP) peptide 158-166 presented by HLA-A*02 (AFP158-166/HLA-A*02)

The AFP158-166 peptide presented by HLA-A*02 is a specific tumor-associated antigen complex utilized as a therapeutic target in hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a glycoprotein normally produced by the fetal liver and yolk sac, but its expression is reactivated in approximately 70-80% of HCC cases (PubMed: 31515456). The specific nonamer peptide FMNKFIYEI (residues 158-166) is generated through proteasomal degradation of intracellular AFP and subsequently presented on the cell surface by the Human Leukocyte Antigen (HLA) A*02:01 molecule (PubMed: 28811304). Because AFP is an intracellular protein, it is inaccessible to conventional monoclonal antibodies; however, this peptide-MHC complex allows for recognition by engineered T-cell receptors (TCRs) or TCR-mimic antibodies (Eureka Therapeutics). Therapeutic candidates like ADP-A2AFP and ET1402L1 are designed to bind this complex to trigger T-cell mediated lysis of malignant hepatocytes (Adaptimmune). This target is particularly valuable due to the high specificity of AFP expression in tumor cells compared to healthy adult tissues, although potential off-tumor effects in regenerating liver tissue remain a clinical consideration.

Other names

AFP158-166 peptideFMNKFIYEI peptideHLA-A*02:01-restricted AFP158-166AFP-MHC complexAFP158

T-cell receptor (TCR) or TCR-mimic binding to the peptide-MHC complex, leading to T-cell activation and targeted cytotoxicity against AFP-expressing tumor cells.