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The macrophage - a novel system to deliver gene therapy to pathological hypoxia.

Abstract
The use of activated macrophages in the treatment of cancer has been largely ineffectual. By 'arming' these cells with the ability to express a therapeutic gene we demonstrate significant advances in the efficacy of this approach. We have used a hypoxia-regulated adenoviral vector to transduce human macrophages with either a reporter or a therapeutic gene encoding human cytochrome P4502B6 (CYP2B6). Infiltration of transduced macrophages into a tumour spheroid results in induction of gene expression. We demonstrate significant tumour cell killing only in the presence of cyclophosphamide via activation by P4502B6 and show that this can be further targeted to tumours through hypoxia regulated gene expression. Gene Therapy (2000) 7, 255-262.
AuthorsL Griffiths, K Binley, S Iqball, O Kan, P Maxwell, P Ratcliffe, C Lewis, A Harris, S Kingsman, S Naylor
JournalGene therapy (Gene Ther) Vol. 7 Issue 3 Pg. 255-62 (Feb 2000) ISSN: 0969-7128 [Print] England
PMID10694803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclophosphamide
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
Topics
  • Adenoviridae (genetics)
  • Aryl Hydrocarbon Hydroxylases
  • Blotting, Western
  • Cyclophosphamide (metabolism)
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 Enzyme System (metabolism)
  • Gene Transfer Techniques
  • Genetic Therapy (methods)
  • Humans
  • Hypoxia (therapy)
  • Macrophages (physiology)
  • Microspheres
  • Oxidoreductases, N-Demethylating (metabolism)

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