Alpha-fetoprotein-derived peptide–MHC class I complex (AFP-pMHC)

Alpha-fetoprotein (AFP) is a major oncofetal protein that is highly expressed during fetal development but typically absent in healthy adults (NIH, 2013; Clinical Cancer Research, 2017). Its re-expression is a characteristic feature of several cancers, particularly hepatocellular carcinoma (HCC) and certain germ cell tumors (NIH, 2024; Clinical Cancer Research, 2017). Although AFP is an intracellular and secreted protein, it is processed into short peptides that are presented on the tumor cell surface by MHC class I molecules, most commonly HLA-A*02:01 (Clinical Cancer Research, 2017; ResearchGate, 2016). These AFP-derived peptide–MHC (pMHC) complexes, such as the immunodominant AFP158–166 epitope, function as specific tumor-associated antigens (NIH, 2001; Frontiers in Immunology, 2020). Therapeutic approaches like TCR-mimic (TCRm) antibodies, CAR-T cells (e.g., ET1402L1), and TCR-T cell therapies (e.g., ADP-A2AFP) are designed to recognize these complexes, enabling the immune system to target and destroy AFP-expressing tumor cells (Eureka Therapeutics, 2022; NIH, 2025). This strategy effectively expands the range of targetable antigens to include intracellular proteins that are otherwise inaccessible to conventional antibody-based therapies (Clinical Cancer Research, 2017; Drug Discovery Trends, 2018).

Other names

AFP-MHC complexAFP-HLA-A*02:01 complexAFP158-166/HLA-A*02:01 complexAlpha-fetoprotein peptide-MHC complexAFP-pMHCAlpha-fetoprotein-derived peptide–MHC class I complexes on tumor cells

T-cell receptor-like recognition and subsequent T-cell mediated cytotoxicity