Alpha-fetoprotein peptide presented by HLA-A*02:01 (AFP/HLA-A*02:01)

The Alpha-fetoprotein (AFP) peptide presented by HLA-A*02:01 is a tumor-associated antigen complex primarily utilized as a target for T-cell receptor (TCR)-based immunotherapies. AFP is a glycoprotein normally produced by the fetal yolk sac and liver, but its expression is reactivated in over 70% of hepatocellular carcinomas (HCC) and some germ cell tumors (PubMed: 28438887). Because AFP is an intracellular protein, it cannot be targeted by traditional antibody-based therapies; however, its degradation products are presented as peptides on the cell surface by the Human Leukocyte Antigen (HLA) system, specifically the HLA-A*02:01 allele (PubMed: 31534005). The most common peptide targeted in this context is AFP158-166 (GMNPVALIQ). Therapeutic strategies, such as ADP-A2AFP and ET1402L1, involve engineering T cells to express TCRs or TCR-mimic receptors that specifically recognize this pMHC complex, leading to the selective lysis of malignant cells (ClinicalTrials.gov: NCT03132792). This approach provides a high degree of specificity for HCC, although potential safety concerns include on-target off-tumor effects if low-level AFP expression exists in non-malignant regenerating liver tissue.

Other names

AFP-MHC complexAFP158-166/HLA-A*02:01AFP542-550/HLA-A*02:01Alpha-fetoprotein-HLA-A2 complexAFP-pMHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation, cytokine release, and targeted lysis of tumor cells.