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

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein primarily expressed during fetal development and significantly downregulated in healthy adults (Source: UniProt P02771). In hepatocellular carcinoma (HCC), AFP is frequently overexpressed and serves as a key diagnostic marker (Source: PubMed PMID: 31515461). Intracellular AFP is processed into peptides, such as the immunodominant AFP158-166 epitope, which are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, typically HLA-A*02:01 (Source: PubMed PMID: 28115573). This peptide-MHC (pMHC) complex is a specific target for immunotherapies like T-cell receptor (TCR) engineered T-cells and TCR-mimic antibodies, which can recognize intracellular antigens not accessible to standard monoclonal antibodies.\n\nDrugs like ADP-A2AFP and ET1402L1 are designed to bind this complex, triggering T-cell mediated destruction of HCC cells (Source: ClinicalTrials.gov NCT03132792). The therapeutic application of this target is limited to patients who are HLA-A*02:01 positive and whose tumors express high levels of AFP. Safety considerations include potential cytokine release syndrome and the risk of on-target off-tumor toxicity if low-level AFP expression exists in non-malignant tissues.

Other names

AFP-HLA complexAFP peptide-HLA-A*02:01 complexAFP158-HLA-A2Alpha-fetoprotein-derived peptide presented by HLAAFP-pMHC

T-cell receptor (TCR) or TCR-mimic binding to the peptide-MHC complex, leading to T-cell activation and cytotoxic lysis of the target cell (Source: PubMed PMID: 28115573).