AAV-Mediated In Vivo CAR Gene Therapy for Targeting Human T Cell Leukemia
AAV-Mediated In Vivo CAR Gene Therapy for Targeting Human T Cell Leukemia
Abstract 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 NCG 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 ex vivo 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. Significance StatementAAV can generate enough CAR cells within the host. That act as a living drug, distributed throughout the body, and persist for weeks, with the ability to recognize and destroy tumor cells.
Wu Zhiwei、Wu Xilin、Xu Shijie、Li Yanlei、Huang Bilian、Zhu Linjing、Nawaz Waqas
Center for Public Health Research, Medical School, Nanjing University||State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University||Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing UniversityCenter for Public Health Research, Medical School, Nanjing University||State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University||Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing UniversityCenter for Public Health Research, Medical School, Nanjing University||State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University||Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing UniversityY-Clone Medical Science Co. Ltd. SuzhouCenter for Public Health Research, Medical School, Nanjing University||State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University||Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing UniversityAbrev BiotechnologyCenter for Public Health Research, Medical School, Nanjing University||State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University||Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University
肿瘤学生物科学研究方法、生物科学研究技术药学
Adeno-associated VirusAAV delivering CAR gene therapyCAR-T therapyT cell leukemiaAAV-CD4+ CAR cellsOff the shelf CAR cells developmentImmunotherapy
Wu Zhiwei,Wu Xilin,Xu Shijie,Li Yanlei,Huang Bilian,Zhu Linjing,Nawaz Waqas.AAV-Mediated In Vivo CAR Gene Therapy for Targeting Human T Cell Leukemia[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.02.15.431201.点此复制
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