Clinical-scale lentiviral vector transduction of PBL for TCR gene therapy and potential for expression in less-differentiated cells.

Published

Journal Article

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 2 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-gamma release and cell lysis. Compared with gamma-retroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population.

Full Text

Cited Authors

  • Yang, S; Rosenberg, SA; Morgan, RA

Published Date

  • November 2008

Published In

Volume / Issue

  • 31 / 9

Start / End Page

  • 830 - 839

PubMed ID

  • 18833004

Pubmed Central ID

  • 18833004

Electronic International Standard Serial Number (EISSN)

  • 1537-4513

International Standard Serial Number (ISSN)

  • 1524-9557

Digital Object Identifier (DOI)

  • 10.1097/CJI.0b013e31818817c5

Language

  • eng