Identification of an HLA‐A*24:02‐restricted α‐fetoprotein signal peptide‐derived antigen and its specific T‐cell receptor for T‐cell immunotherapy
| Autor: | Yaolong Chen, Yi Li, Wu Wanli, Zhenjuan Li, Gong Haiping, Yingyi Mei, Yu Xiaohong, Jianting Cheng, Shi Zhong, Liu Qiuping, Hongjun Zheng |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Signal peptide Carcinoma Hepatocellular Immunology Receptors Antigen T-Cell Gene Expression HLA-A24 Antigen Human leukocyte antigen Protein Sorting Signals Transfection Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine Antigen Antigens Neoplasm Cell Line Tumor Immunology and Allergy Humans Amino Acid Sequence Receptor neoplasms Binding Sites Chemistry T-cell receptor Liver Neoplasms Original Articles Hep G2 Cells digestive system diseases Coculture Techniques Healthy Volunteers HLA-A 030104 developmental biology Cancer research Immunotherapy alpha-Fetoproteins Alpha-fetoprotein Oligopeptides 030215 immunology Protein Binding T-Lymphocytes Cytotoxic |
| Zdroj: | Immunology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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