共 39 条
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
论文数: 0 引用数: 0
h-index: 0
机构:
NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

Rosenberg, Steven A.
论文数: 0 引用数: 0
h-index: 0
机构:
NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

Morgan, Richard A.
论文数: 0 引用数: 0
h-index: 0
机构:
NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
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.
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收藏
页码:830 / 839
页数:10
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