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

The Alpha-fetoprotein (AFP)-derived peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a therapeutic target in oncology, particularly for hepatocellular carcinoma (HCC) [1, 4]. AFP is an oncofetal glycoprotein that is highly expressed during fetal development but becomes transcriptionally silenced shortly after birth; however, it is frequently reactivated and overexpressed in HCC and certain germ cell tumors [1]. The specific peptide fragment, typically the 9-amino acid sequence AFP158-166 (FMNKFIYEI), is processed by the proteasome and transported to the cell surface where it is presented by the HLA-A*02:01 molecule [4]. This complex is recognized by specialized T-cell receptors (TCRs), making it an ideal target for adoptive cell therapies such as TCR-engineered T-cells (TCR-T) and TCR-mimic antibodies [2, 3]. Because AFP is not significantly expressed in healthy adult tissues, targeting this pMHC complex allows for the selective destruction of tumor cells while minimizing damage to normal liver tissue [2]. Clinical development of therapies targeting this complex, such as ADP-A2AFP and ET1402L1, has focused on patients who are both HLA-A*02:01 positive and have AFP-secreting tumors [2, 3]. Citations: [1] UniProt P02771; [2] Adaptimmune Therapeutics (NCT03132792); [3] Eureka Therapeutics (NCT03349255); [4] PubMed (PMID: 11060014).

Other names

AFP158-166/HLA-A*02:01Alpha-fetoprotein peptide-MHC complexAFP-pMHCFMNKFIYEI-HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted lysis of AFP-expressing tumor cells.