Alpha-fetoprotein-derived peptide-HLA class I complex (AFP-peptide/HLA complex)

Alpha-fetoprotein (AFP) is a fetal glycoprotein that is highly expressed during embryonic development but significantly downregulated after birth. In adults, its re-expression is a hallmark of certain malignancies, particularly hepatocellular carcinoma (HCC) and germ cell tumors. Intracellular AFP is proteolytically processed into short peptide fragments, which are then transported to the cell surface and presented by Human Leukocyte Antigen (HLA) class I molecules, such as HLA-A*02:01. This AFP-peptide/HLA complex acts as a specific molecular signature for tumor cells, allowing them to be recognized by the cellular immune system. Therapeutic strategies targeting this complex include TCR-engineered T-cells (TCR-T), such as ADP-A2AFP, and "TCR-like" chimeric antigen receptor (CAR) T-cells that can bind the MHC-restricted peptide with high affinity. Additionally, dendritic cell-based vaccines use these peptides to prime and expand endogenous AFP-specific cytotoxic T lymphocytes. By focusing on the peptide-MHC complex rather than the secreted protein, these therapies can effectively target the intracellular reservoir of AFP within tumor cells. Clinical evidence has shown that targeting this complex can lead to objective clinical responses in patients with advanced, treatment-refractory liver cancer.

Other names

AFP-MHC complexAFP-HLA complexAFP-derived epitopesAFP158-166/HLA-A*02:01 complexAlpha-fetoprotein-derived peptides presented on HLA class I

T-cell mediated cytotoxicity; recognition of the specific peptide-HLA complex by engineered T-cell receptors (TCRs) or TCR-like chimeric antigen receptors (CARs) leads to T-cell activation, cytokine release, and selective lysis of AFP-expressing tumor cells.