Gene transfer into human dendritic antigen-presenting cells by vaccinia virus and adenovirus vectors

Massimo Di Nicola, Salvatore Siena, Marco Bregni, Paolo Longoni, Michele Magni, Marco Milanesi, Paola Matteucci, Roberta Mortarini, Andrea Anichini, Giorgio Parmiani, Ingo Drexler, Volker Erfle, Gerd Sutter, A. Massimo Gianni

Research output: Contribution to journalArticle

Abstract

In a search for means to deliver exogenous gene(s) into human dendritic cells (DCs) from the perspective of tumor-specific vaccination, we have evaluated two recombinant viruses, both of which carry a reporter gene which is namely a modified vaccinia virus Ankara (MVA) and an adenovirus, as possible expression vectors. The recombinant MVA-P11LZ vector carries the Escherichia coli lacZ gene coding for the enzyme β-galactosidase, and the recombinant Ad-MFG-AP vector carries a modified membrane-exposed alkaline phosphatase (AP) gene. DCs were generated ex vivo in the presence of tumor necrosis factor-α, granulocyte macrophage colony-stimulating factor, stem cell factor, and flk-2/flt-3 ligand taken from CD34+ hematopoietic progenitors that were mobilized into the peripheral blood of cancer patients treated with high-dose cyclophosphamide and filgrastim. The target cells used for gene delivery were either CD34+ cells that had been subsequently induced to differentiate into mature DCs or DCs transduced after ex vivo generation from CD34+ cells. The results showed that: (a) infection of CD34+ cell derived-DCs (mature DCs) with either viral vector resulted in the efficient synthesis of recombinant protein, and (b) CD34+ cells were permissive for the expression of the recombinant reporter gene after infection with Ad-MFG-AP but not after infection with MVA-P11LZ. In conclusion, these results suggest that vaccinia and adenovirus vectors are candidate to act as vehicles in genetically engineering human DCs.

Original languageEnglish
Pages (from-to)350-356
Number of pages7
JournalCancer Gene Therapy
Volume5
Issue number6
Publication statusPublished - 1998

Keywords

  • Adenovirus
  • CD34 cells
  • Dendritic cells
  • Modified vaccinia Ankara

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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