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鉴定针对瘤免疫疗法的HPV-E7特异性TCRs

Xiaowen Li¹, Wenling Wang¹, Jie Wang²

¹Institute 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.

Molecular immunology

|May 25, 2024

概括

研究人员在HLA-A11:01小鼠中确定了两个有前途的T细胞受体 (TCRs),向人类乳头瘤病毒 (HPV) E7蛋白. 这些TCR显示出开发针对HPV诱导瘤的新免疫疗法的潜力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
病毒学病毒学

背景情况:

人类乳头瘤病毒 (HPV) 瘤原蛋白E7在与HPV相关的瘤中表达.
基于T细胞受体 (TCR) 的免疫疗法,特别是TCR工程T (TCR-T) 细胞,是针对HPV诱导的瘤的一种有前途的方法.

研究的目的:

从HLA-A11:01转基因小鼠中识别HPV-E7特定的TCR.
评估这些已识别的TCR在T细胞基础免疫疗法的治疗潜力.

主要方法:

使用E789-97/HLA-A11:01四聚合物进行单细胞分类和测序.
通过初级T细胞的lentiviral转导生成TCR-T细胞.
评估TCR响应,细胞因子分泌和多功能反应.

主要成果:

确定了两个具有特异性结合E789-97/HLA-A11:01的主导TCR.
TCR-T细胞表现出显著的响应能力和CD8+依赖的细胞因子分泌.
鉴定到的TCR在特定刺激时表现出多功能反应.

结论:

这两种已识别的TCR是开发新型免疫疗法的有希望的候选者.
这些TCR在瘤免疫治疗中针对HLA-A11:01的背景下准HPV-E7.

关键词:

在 HLA-A*11:01 中.人类乳头瘤病毒的人类乳头瘤病毒型蛋白质E7 型蛋白质E7 T细胞受体受体的 T 细胞受体.这是一种TCR-T细胞疗法.

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