Clinical-scale lentiviral vector transduction of pbl for tcr gene therapy and potential for expression in less-differentiated cells

Shicheng Yang, Steven A. Rosenberg, Richard A. Morgan

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)830-839
Number of pages10
JournalJournal of Immunotherapy
Volume31
Issue number9
DOIs
StatePublished - 2008

Keywords

  • Adoptive immunotherapy
  • Gene therapy
  • Lentivirus
  • T-cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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