Alpha-fetoprotein peptide-MHC class I complex (AFP-MHC)

The Alpha-fetoprotein (AFP) peptide-MHC class I complex is a tumor-associated antigen target primarily utilized in the development of adoptive T-cell therapies for hepatocellular carcinoma (HCC) (Adaptimmune, 2021; NIH, 2025). AFP is an oncofetal protein that is highly expressed during fetal development but is largely absent in healthy adult tissues, making it a highly specific marker for certain malignancies (Eureka Therapeutics, 2022; NIH, 2025). Intracellular AFP is processed into short peptides, such as the immunodominant AFP158-166 epitope, which are then presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 (Hepatology, 2018; Clin Cancer Res, 2016). These complexes are specifically recognized by T-cell receptors (TCRs) on cytotoxic T lymphocytes, which then mediate the targeted lysis of the tumor cells (Hepatology, 2018; MDPI, 2022). Because AFP is an intracellular and secreted protein, it is inaccessible to conventional antibody therapies; however, targeting the pMHC complex allows for the therapeutic recognition of these intracellular antigens (Clin Cancer Res, 2016; Eureka Therapeutics, 2022). Current clinical strategies include TCR-engineered T-cells (TCR-T) and TCR-mimic (TCRm) chimeric antigen receptor T-cells (CAR-T), such as ADP-A2AFP and ET1402L1, which have demonstrated promising antitumor activity and a manageable safety profile in patients with advanced liver cancer (Adaptimmune, 2021; Targeted Oncology, 2021).

Other names

AFP-MHC complexAFP peptide-HLA complexAFP158-166/HLA-A*02:01 complexAlpha-fetoprotein-derived peptide–MHC class I complexAFP-pMHC

Engineered T-cells (TCR-T or TCRm CAR-T) express receptors that specifically bind to the AFP peptide presented by MHC class I molecules on the tumor cell surface, leading to T-cell activation, cytokine release, and targeted cytotoxicity.