Functional transfer of CD40L gene in human B-cell precursor ALL blasts by second-generation SIN lentivectors

Gene Ther. 2004 Jan;11(1):85-93. doi: 10.1038/sj.gt.3302141.

Abstract

Three different second-generation lentiviral self-inactivating vectors containing CMV, EF1alpha and PGK promoter, respectively, and all carrying the exogenous GFP gene, were compared for expression in human B-cell precursor ALL blasts. At a comparable percentage of transduction and vector DNA copy number, CMV clearly showed better efficiency of transcription. Human bone marrow stromal cells were favored compared to the MRC-5 cell line, as support for cell viability during infection. Cells were infected and analyzed after variable culture times ranging from 4 to 12 days, to reduce the possibility of pseudotransduction. In 10/14 samples, we detected more than 20% GFP-positive cells after exposure to high-titer viral supernatants. We then tested a similar vector carrying the human CD40L cDNA and, in similar infection conditions, obtained more than 20% transduction in 6/6 samples. The levels of transduction obtained were sufficient to induce the upregulation of CD83 molecule in cocultured immature dendritic cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Ligand / genetics*
  • Cell Line, Tumor
  • Cytomegalovirus / genetics
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Green Fluorescent Proteins
  • Humans
  • Lentivirus / genetics*
  • Luminescent Proteins / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Promoter Regions, Genetic
  • Transcription, Genetic
  • Transduction, Genetic / methods

Substances

  • Luminescent Proteins
  • CD40 Ligand
  • Green Fluorescent Proteins