嵌合抗原受体
遗传增强
体内
细胞疗法
白血病
人性化鼠标
免疫学
癌症研究
医学
生物
T细胞
干细胞
基因
免疫系统
细胞生物学
生物技术
生物化学
作者
Waqas Nawaz,Bilian Huang,Shijie Xu,Yanlei Li,Linjing Zhu,Hu Yiqiao,Zhiwei Wu,Xi-Lin Wu
标识
DOI:10.1038/s41408-021-00508-1
摘要
Chimeric antigen receptor (CAR) T-cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T-cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus (AAV) vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NOD.Cg-Prkdcscid Il2rgem26/Nju tumor mouse model of human T-cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo-generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the β processes of traditional CAR T-cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.
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