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	High-efficiency viral gene delivery for T lymphocytes engineering using metabolic bioorthogonal strategy
	Fangfang Wang; Yutong Han; Yingmei Luo; Lintao Cai; Yifan Ma; Hong Pan
	2018
会议日期	2018
会议地点	上海
英文摘要	Engineered T cells have been used as treatment for tumors which shows promising clinical results. However, the outcomes have yet been tempered by the manufacturing process due to low delivery efficiency of exogenous gene. Herein, we utilized glycometabolic labeling and bioorthogonal chemistry to establish a highly efficient viral transduction system for human primary T lymphocytes. we synthesized and optimized DBCO-PEG4-NHS conjugated PEI1.8K (PEI-DBCO), and utilized the glycometabolic labeling to incorporate azide groups onto the surface of T cells by administration with azide-conjugated glucose Ac4GlcNAz. PEI-DBCO packaged viruses were facilitated to the azide-labeled T cell infection via bioorthogonal targeting, and rising the lentiviral infection efficiency up to 80% without damping T cell activities. In particularly, PEI-DBCO facilitated viral transduction system significantly increased amount of CD19 specific CAR T cells, and enhanced anti-tumor cytokine secretion. Administration of CAR T cells prepared by PEI-DBCO facilitated viral transduction system exerted better curative effects in the humanized B lymphoma bearing mice, comparing with those mice treated with conventional manufactured CAR T cells both in vitro and in vivo. This novel cell gene delivery technique based on glycometabolic bioorthogonal chemistry, displays powerful capability in engineering of primary T lymphocytes, especially in the clinical CAR T cell manufacture and immunotherapy.
语种	英语
内容类型	会议论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/14748]
专题	深圳先进技术研究院_医药所
推荐引用方式 GB/T 7714	Fangfang Wang,Yutong Han,Yingmei Luo,et al. High-efficiency viral gene delivery for T lymphocytes engineering using metabolic bioorthogonal strategy[C]. 见:. 上海. 2018.

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