Zhenjuan Li et al, Identification of a HLA‐A*24:02‐restricted alpha‐fetoprotein signal peptide derived antigen and its specific T cell receptor for T cell immunotherapy. https://doi.org/10.1111/imm.13168 Dec. 17/2019
Hepatocellular carcinoma (HCC) is the most common type of liver cancer with limited treatments. Asia has the highest HCC incidence rates; China accounts for over 50% of all HCC cases worldwide. T‐cell receptor (TCR)‐engineered T cell immunotherapies specific for HLA‐A*02:01 restricted alpha‐fetoprotein (AFP) peptide have shown encouraging results in clinics. HLA‐A*24:02 is more common than HLA‐A*02:01 in Asian countries including China. Here we identified a novel HLA‐A*24:02 restricted peptide KWVESIFLIF (AFP2‐11) located in AFP signal peptide domain by mass spectrometric analysis of HLA bound peptides from HepG2 cells. A TCR (KWV3.1) specific for AFP2‐11/HLA‐A*24:02 was isolated from peripheral blood mononuclear cells (PBMCs) of a healthy donor. The binding affinity of soluble KWV3.1 to its antigen was determined to be ~55 μM, within the affinity range of native TCRs for self‐antigens. KWV3.1 transduced T cells could specifically activate and kill AFP2‐11 pulsed T2‐A24 cells and AFP+/HLA‐A*24:02+ tumor cell lines, demonstrating that AFP2‐11 can be naturally presented on the surface of AFP+ tumor cell lines. The newly identified antigenic peptide can provide a novel target for immunotherapeutic strategies for AFP+/HLA‐A*24:02+ HCC patients.