B7-H3嵌合抗原受体重定向T细胞靶向间变性淋巴瘤激酶阳性间变性大细胞淋巴瘤
B7-H3 Chimeric Antigen Receptor Redirected T Cells Target Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma.
作者信息
Zi Zhenguo, Zhao Haihong, Wang Huanyu, Ma Xiaojing, Wei Fang
机构信息
Sheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200032, China.
Department of Obstetrics and Gynecology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
出版信息
Cancers (Basel). 2020 Dec 17;12(12):3815. doi: 10.3390/cancers12123815.
Potent CAR-T therapies that target appropriate antigens can benefit the treatment of anaplastic lymphoma kinase-positive (ALK) anaplastic large cell lymphoma (ALCL), which is the most common subtype of T cell lymphoma. In this study, we observed overexpression of B7-H3 in ALCL cell lines derived from clinical samples and differential expression of B7-H3 in an ALK-induced T cell transformation model. A B7-H3-redirected CAR based on scFv from mAb 376.96 was developed. B7-H3 CAR-T cells showed strong cytotoxicity and cytokine secretion against target ALCL cells (SUP-M2, SU-DHL-1, and Karpas 299) in vitro. Furthermore, the B7-H3 CAR-T cells exhibited proliferative capacity and a memory phenotype upon repeated antigen stimulation. We demonstrated that B7-H3 CAR-T cells could promptly eradicate ALCL in murine xenografts. Taken together, B7-H3 is a novel and promising target in ALCLs and B7-H3 CAR-T may be a viable treatment option for ALCL.
靶向合适抗原的强效嵌合抗原受体（CAR）-T细胞疗法可改善间变性淋巴瘤激酶阳性（ALK）间变性大细胞淋巴瘤（ALCL）的治疗，ALCL是T细胞淋巴瘤最常见的亚型。在本研究中，我们观察到临床样本来源的ALCL细胞系中B7-H3的过表达以及ALK诱导的T细胞转化模型中B7-H3的差异表达。基于单克隆抗体376.96的单链抗体片段（scFv）构建了一种重定向B7-H3的CAR。B7-H3 CAR-T细胞在体外对靶ALCL细胞（SUP-M2、SU-DHL-1和Karpas 299）表现出强大的细胞毒性和细胞因子分泌能力。此外，B7-H3 CAR-T细胞在反复抗原刺激后表现出增殖能力和记忆表型。我们证明B7-H3 CAR-T细胞能够迅速根除小鼠异种移植瘤中的ALCL。综上所述，B7-H3是ALCL中一个新的且有前景的靶点，B7-H3 CAR-T可能是ALCL的一种可行治疗选择。
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