Identification of an HLA-A*24:02-restricted α-fetoprotein signal peptide-derived antigen and its specific T-cell receptor for T-cell immunotherapy.,Immunology

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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.
Immunology ( IF 6.4 ) Pub Date : 2020-01-10 , DOI: 10.1111/imm.13168
Zhenjuan Li _{1,

2,

3} , Haiping Gong ₂ , Qiuping Liu ₂ , Wanli Wu ₂ , Jianting Cheng ₂ , Yingyi Mei ₂ , Yaolong Chen ₂ , Hongjun Zheng ₂ , Xiaohong Yu ₂ , Shi Zhong ₂ , Yi Li _{2,

3}

Affiliation

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 μm, 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.

更新日期：2020-03-26

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