Alpha-fetoprotein peptide presented by HLA-A*02:01 (AFP/HLA-A*02:01)

The Alpha-fetoprotein (AFP) peptide presented by HLA-A*02:01 is a tumor-associated antigen complex that serves as a critical target for advanced cancer immunotherapies, specifically in hepatocellular carcinoma (HCC). AFP is an oncofetal glycoprotein primarily produced during fetal development; however, its expression is reactivated in adult life within malignant liver cells and certain germ cell tumors, making it a classic biomarker for malignancy (Butterfield et al., 2001, J. Immunol.). Because AFP is an intracellular and secreted protein, it cannot be targeted by traditional CAR-T cells that require surface-bound proteins. Instead, intracellular AFP is processed into short peptides, such as the immunodominant AFP158-166 (FMNKFIYEI) fragment, and presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (Adaptimmune, 2023). This presentation allows the complex to be recognized by engineered T-cell receptors (TCRs) or TCR-mimic antibodies, facilitating the targeted destruction of cancer cells. Clinical developments, including TCR-T cell therapies like ADP-A2AFP, leverage this mechanism to provide a highly specific immune response against HCC (ClinicalTrials.gov, NCT03132792). Safety considerations for targeting this complex include potential on-target off-tumor effects in tissues with low-level AFP expression and the management of systemic inflammatory responses like cytokine release syndrome.

Other names

AFP-MHC complexAFP-HLA-A2 complexAFP158-166/HLA-A*02:01Alpha-fetoprotein-derived peptide-HLA-A*02:01 complexAFP-pMHC

T-cell receptor (TCR) mediated recognition and lysis of antigen-presenting cells; TCR-engineered T-cell therapy; TCR-mimic antibody-based CAR-T therapy.