CD4 靶向 T 细胞可快速诱导 T 细胞淋巴瘤小鼠缓解。
CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma.
机构信息
Department of Hematology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Department of Hematology, Anhui Provincial Children's Hospital, Anhui Province, China.
出版信息
Biomed Res Int. 2021 Mar 27;2021:6614784. doi: 10.1155/2021/6614784. eCollection 2021.
OBJECTIVE
To explore the immune cell therapy for T cell lymphoma, we developed CD4-specific chimeric antigen receptor- (CAR-) engineered T cells (CD4CART), and the cytotoxic effects of CD4CART cells were determined in vitro and in vivo.
METHODS
CD4CART cells were obtained by transduction of lentiviral vector encoding a single-chain antibody fragment (scFv) specific for CD4 antigen, costimulatory factor CD28 fragment, and intracellular signal transduction domain of CD3 fragments. Control T cells were obtained by transduction of reporter lentiviral vector. The cytotoxicity, tumor growth, and survival rate of mice with T cell lymphoma were analyzed after adoptive T cell transfer in vivo.
RESULTS
CD4CART cells had potent cytotoxic activity against CD4+ T1301 tumor T cells in a concentration-dependent manner. In addition, adoptive CD4CART cell transfer significantly suppressed tumor growth and improved animal survival with T cell lymphoma, compared to the mice who received control T cells and PBS.
CONCLUSION
CD4CART cells have potent cytotoxic effects on T cell lymphoma. The study provided an experimental basis for CD4CART-mediated therapy of T cell lymphoma.
目的
为了探索 T 细胞淋巴瘤的免疫细胞治疗，我们开发了 CD4 特异性嵌合抗原受体-（CAR-）工程 T 细胞（CD4CART），并在体外和体内测定了 CD4CART 细胞的细胞毒性作用。
方法
通过转导编码针对 CD4 抗原、共刺激因子 CD28 片段和 CD3 片段胞内信号转导域的单链抗体片段（scFv）的慢病毒载体获得 CD4CART 细胞。通过转导报告基因慢病毒载体获得对照 T 细胞。分析体内过继转移 T 细胞后 T 细胞淋巴瘤小鼠的细胞毒性、肿瘤生长和存活率。
结果
CD4CART 细胞以浓度依赖的方式对 CD4+T1301 肿瘤 T 细胞具有强大的细胞毒性。此外，与接受对照 T 细胞和 PBS 的小鼠相比，过继性 CD4CART 细胞转移显著抑制了 T 细胞淋巴瘤的肿瘤生长并提高了动物存活率。
结论
CD4CART 细胞对 T 细胞淋巴瘤具有强大的细胞毒性作用。该研究为 CD4CART 介导的 T 细胞淋巴瘤治疗提供了实验基础。
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