Alpha-fetoprotein peptide–Human leukocyte antigen complex (AFP-HLA complex)

The Alpha-fetoprotein (AFP) peptide–Human leukocyte antigen (HLA) complex is a tumor-specific antigen presentation target primarily utilized in the treatment of hepatocellular carcinoma (HCC) (Butterfield et al., 2001; PMID: 11156516). AFP is an oncofetal protein that is highly expressed during fetal development but is transcriptionally silenced in healthy adult tissues, except for low-level expression in the liver (Mizejewski, 2001; PMID: 11336486). In many HCC cases, AFP is significantly overexpressed and undergoes intracellular processing into peptides, such as the AFP158-166 epitope (FMNKFIYEI), which are then presented on the cell surface by HLA-A*02:01 molecules (Liu et al., 2017; PMID: 28100605). This peptide-MHC (pMHC) complex serves as a critical target for T-cell receptor (TCR)-based immunotherapies, including TCR-engineered T cells (TCR-T) and TCR-mimic (TCRm) antibodies, which can recognize intracellular antigens that are otherwise inaccessible to conventional antibody therapies (Adaptimmune, 2020; Eureka Therapeutics, 2021). Drugs like ADP-A2AFP are designed to bind this complex with high specificity to induce T-cell mediated lysis of tumor cells (ClinicalTrials.gov, NCT03132792). The therapeutic utility of this target is contingent upon the patient's HLA type and the level of AFP expression within the tumor (He et al., 2022; PMID: 35641486). Safety monitoring is essential due to the potential for cytokine release syndrome and the risk of targeting regenerating liver tissue that may transiently express AFP.

Other names

AFP-MHC complexAFP peptide-MHCAFP158-166/HLA-A*02:01 complexAlpha-fetoprotein-MHC class I complexAFP158-HLA-A2

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex, leading to T-cell activation, cytokine release, and direct lysis of the target tumor cell (Adaptimmune, 2020; Liu et al., 2017; PMID: 28100605).