重编程工程化自体 T 细胞以克服 Merkel 细胞癌患者的耐药性
Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
用于肿瘤免疫治疗的 HPV-E7 特异性 TCR 鉴定
英文原题：Identification of HPV-E7 specific TCRs for tumor immunotherapy.
查看英文原题
Identification of HPV-E7 specific TCRs for tumor immunotherapy.
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中文摘要
人乳头瘤病毒（HPV）的致癌蛋白 E7 在 HPV 相关肿瘤中持续表达，可作为 T 细胞受体（TCR）免疫疗法的潜在靶点。过继转移 TCR 工程化 T（TCR-T）细胞已显示出治疗 HPV 诱发肿瘤的潜力。
本研究利用 E7 89–97/HLA-A11:01 四聚体，通过单细胞分选和测序，从 HLA-A11:01 转基因小鼠中鉴定 HPV-E7 特异性 TCR。
研究发现两种优势 TCR，可特异性结合由 HLA-A*11:01 呈递的 E7 89–97 肽。通过用携带 TCR 基因的慢病毒感染原代 T 细胞制备 TCR-T 细胞；这两种 TCR 均表现出显著应答，并显示出 CD8+ 依赖性细胞因子分泌特征。
进一步分析细胞因子谱发现，受到特异性刺激后，两种 TCR 均可产生多功能应答。这些发现提示，这两种 TCR 是有前景的候选分子，可用于开发靶向 HLA-A11:01 限制性 HPV-E7 的肿瘤免疫治疗药物。
展开英文摘要原文
The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors.
This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E7 89-97 /HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E7 89-97 presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics.
Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation.
These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.
论文信息
- 作者
- Li X、Wang W、Wang J、Jiang M、He J、Tan S
- 第一作者单位
- Institute of Physical Science and Information, Anhui University, Hefei, Anhui, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.China
- 通讯作者单位
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China; Shenzhen Children's Hospital, Shenzhen, Guangdong, China. Electronic address: tansg@im.ac.cn.China
- 期刊
- Molecular immunology2024 Jul
- 原文标识
- PubMed 38795685 · DOI 10.1016/j.molimm.2024.05.006