Alpha-fetoprotein (AFP) peptide–HLA-A*02:01 complex (AFP–HLA-A*02:01)

The Alpha-fetoprotein (AFP) peptide–HLA-A*02:01 complex is a tumor-associated antigen target primarily utilized in the development of immunotherapies for hepatocellular carcinoma (HCC). AFP is a fetal glycoprotein that is normally silenced after birth but becomes highly overexpressed in the majority of liver cancers [1, 13]. Because AFP is an intracellular or secreted protein, it is not accessible to traditional surface-binding antibodies; however, it is processed into peptides (most notably the AFP158-166 epitope) and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01 [2, 6]. This presentation allows the complex to be targeted by T-cell receptor (TCR)-engineered T-cells or TCR-like chimeric antigen receptor (CAR) T-cells, such as ADP-A2AFP and ET1402L1 [5, 15]. These therapies are designed to selectively recognize and kill HLA-A*02:01-positive tumor cells that express AFP, while sparing healthy adult tissues where AFP expression is minimal [2, 11]. Clinical trials have demonstrated that targeting this complex can induce significant antitumor responses, including complete remissions in patients with advanced HCC [15, 17].

Other names

AFP158-166/HLA-A*02:01AFP-MHC complexAlpha-fetoprotein-derived peptide presented by HLA-A*02:01AFP/MHC class I complex (AMC)FMNKFIYEI–HLA-A*02:01

T-cell receptor (TCR) or chimeric antigen receptor (CAR) mediated recognition of the specific AFP peptide presented by HLA-A*02:01, leading to T-cell activation, cytokine release, and targeted lysis of tumor cells [1, 2, 16].