Alpha-fetoprotein peptide-HLA-A*02 complex (AFP/HLA-A*02)

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein primarily expressed during fetal development and highly overexpressed in hepatocellular carcinoma (HCC) and other germ cell tumors [2, 5]. As an intracellular and secreted protein, AFP is not accessible to conventional antibody therapies; however, it is processed into short peptides that are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, such as HLA-A*02 [3, 5]. The AFP peptide-HLA-A*02 complex (specifically the immunodominant AFP158-166 epitope) serves as a highly specific tumor-associated antigen (TAA) that can be recognized by engineered T-cell receptors (TCRs) or TCR-mimic antibodies [5, 12]. Therapeutic strategies targeting this complex, including TCR-T cell therapies (e.g., ADP-A2AFP) and TCR-mimic CAR-T cell therapies (e.g., ET1402L1), aim to redirect the patient's immune system to selectively eliminate AFP-expressing malignant cells [7, 9, 22]. Clinical development of these therapies requires precise patient selection based on both HLA-A*02:01 positivity and significant AFP expression levels to ensure efficacy and minimize off-target risks [7, 15]. Recent clinical trials have demonstrated manageable safety profiles and preliminary evidence of antitumor activity in advanced liver cancer patients [15, 22].

Other names

AFP-MHC complexAFP-HLA complexAFP158-166/HLA-A*02:01FMNKFIYEI/HLA-A*02:01AFP-HLA-A2 complexAlpha-fetoprotein peptide presented by Human leukocyte antigen A*02

Engineered T-cell receptor (TCR) or TCR-mimic chimeric antigen receptor (CAR) binding to the peptide-MHC complex, leading to T-cell activation, cytokine release, and targeted lysis of AFP-expressing tumor cells [2, 5, 12].