Abstract
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°C for 2舁h) 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-γ release and cell lysis. Compared with gamma-retroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population.
Original language | English (US) |
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Pages (from-to) | 830-839 |
Number of pages | 10 |
Journal | Journal of Immunotherapy |
Volume | 31 |
Issue number | 9 |
DOIs | |
State | Published - 2008 |
Externally published | Yes |
Keywords
- Adoptive immunotherapy
- Gene therapy
- Lentivirus
- T-cell receptor
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology
- Cancer Research