Alpha-fetoprotein-derived peptide epitope presented by HLA-A24 (AFP/HLA-A24)

The Alpha-fetoprotein (AFP)-derived peptide epitope presented by HLA-A24 is a tumor-associated antigen complex primarily utilized in the immunotherapy of hepatocellular carcinoma (HCC). AFP is an oncofetal protein that is typically silenced after birth but becomes reactivated and overexpressed in various malignancies, including HCC and certain germ cell tumors (PMID: 31533485). Within the tumor cell, AFP is proteolytically processed into short peptide fragments, such as the immunodominant AFP469 or AFP357 peptides, which are then presented on the cell surface by the Human Leukocyte Antigen (HLA)-A24 molecule (PMID: 15150595). This specific peptide-MHC complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune-mediated attack against the cancer cell. Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies like ADP-A2AFP, are designed to bind this complex with high affinity to eliminate tumor cells (PMID: 33033114). Given that HLA-A24 is one of the most common HLA alleles in East Asian populations, this target represents a significant opportunity for precision oncology in regions with high HCC prevalence. Clinical development focuses on ensuring specificity to avoid off-target effects on normal tissues that might express low levels of AFP, such as regenerating liver tissue.

Other names

AFP-derived CTL epitopeHLA-A*24:02-restricted AFP peptideAFP peptide-MHC complexAlpha-fetoprotein antigen

Engineered T-cell receptors (TCRs) or vaccines target the peptide-MHC complex to induce MHC-restricted, antigen-specific cytotoxicity by CD8+ T cells against AFP-expressing malignant cells.