Clinical-scale Lentiviral Vector Transduction of PBL for TCR Gene Therapy and Potential for Expression in Less-differentiated Cells

被引:31
作者
Yang, Shicheng [1 ]
Rosenberg, Steven A. [1 ]
Morgan, Richard A. [1 ]
机构
[1] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
关键词
lentivirus; T-cell receptor; adoptive immunotherapy; gene therapy;
D O I
10.1097/CJI.0b013e31818817c5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors because of their ability to transduce nondividing cells, their resistance to gene silencing, and a lack of integration site preference. In this study, we used VSV-G pseudotype third generation lentiviral vectors harboring specific antitumor T-cell receptor (TCR) to establish clinical-scale lentiviral transduction of peripheral blood lymphocyte (PBL). Spinoculation (1000g, 32 degrees C for 2h) in the presence of protamine sulfate represents the most efficient and economical approach to transduce a large number of PBLs compared with RetroNectin-based methods. Up to 20 million cells per well of a 6-well plate were efficiently transduced and underwent an average 50-fold expansion in 2 weeks. TCR transduced PBL-mediated specific antitumor activities including interferon-7 release and cell lysis. Compared with gammaretroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population.
引用
收藏
页码:830 / 839
页数:10
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