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

The Alpha-fetoprotein-derived peptide–HLA class I complex is a specialized molecular target used in cancer immunotherapy, particularly for treating hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is an oncofetal protein that is highly expressed during fetal development and by certain tumor cells, but is largely absent in healthy adult tissues (Butterfield et al., 1999, Journal of Immunology). Because AFP is an intracellular protein, it is not accessible to standard antibody therapies; however, it is processed into short peptides, such as AFP158–166, which are then presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, most commonly HLA-A*02:01 (Liu et al., 2017, Gastroenterology). This peptide-MHC complex acts as a unique 'flag' that can be recognized by engineered T-cell receptors (TCRs). Therapeutic strategies, such as TCR-engineered T-cell (TCR-T) therapy, utilize these receptors to specifically bind the AFP-peptide–HLA complex and trigger a cytotoxic immune response against the cancer cells (Adaptimmune Therapeutics plc, 2020). Clinical success depends on the patient possessing the specific HLA allele and the tumor maintaining high levels of AFP expression. Potential challenges include the risk of cytokine release syndrome and the necessity of ensuring the TCR does not cross-react with similar peptides found on vital organs.

Other names

AFP-MHC complexAFP158-166 peptide-HLA-A*02:01 complexAlpha-fetoprotein peptide-MHC complexAFP-HLA-A2 complex

T-cell receptor (TCR) mediated recognition of the specific AFP peptide presented by HLA class I molecules, leading to T-cell activation, cytokine release, and directed lysis of AFP-expressing tumor cells.