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Identification of an HLA‐A*24:02‐restricted α ‐fetoprotein signal peptide‐derived antigen and its specific T‐cell receptor for T‐cell immunotherapy
Author(s) -
Li Zhenjuan,
Gong Haiping,
Liu Qiuping,
Wu Wanli,
Cheng Jianting,
Mei Yingyi,
Chen Yaolong,
Zheng Hongjun,
Yu Xiaohong,
Zhong Shi,
Li Yi
Publication year - 2020
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13168
Subject(s) - t cell receptor , human leukocyte antigen , antigen , biology , immunotherapy , t cell , cytotoxic t cell , peripheral blood mononuclear cell , alpha fetoprotein , tumor antigen , microbiology and biotechnology , hepatocellular carcinoma , immunology , cancer research , immune system , in vitro , biochemistry
Summary 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 human leukocyte antigen (HLA) ‐A*02:01‐restricted α ‐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 (AFP 2–11 ) located in AFP signal peptide domain by mass spectrometric analysis of HLA‐bound peptides from HepG2 cells. A TCR (KWV3.1) specific for AFP 2–11 ‐HLA‐A*24:02 was isolated from peripheral blood mononuclear cells of a healthy donor. The binding affinity of soluble KWV3.1 to its antigen was determined to be ~55 μ m , within the affinity range of native TCRs for self‐antigens. KWV3.1‐transfected T cells could specifically activate and kill AFP 2–11 pulsed T2‐A24 cells and AFP + HLA‐A*24:02 + tumor cell lines, demonstrating that AFP 2–11 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 patients with AFP + HLA‐A*24:02 + HCC.