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Genetic manipulation of drug sensitivity in haematopoietic cells

Published online by Cambridge University Press:  23 September 2004

Thomas Southgate
Affiliation:
Cancer Research UK Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Leslie J. Fairbairn
Affiliation:
Cancer Research UK Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.
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Abstract

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The haematopoietic system can be manipulated genetically to increase either its resistance to drugs or its sensitivity to certain agents. Gene transfer and expression of specific drug-resistance factors might protect haematopoietic function during antitumour chemotherapy, or allow enrichment of gene-modified cells in vivo. By contrast, gene transfer of a prodrug activator, to confer sensitivity to otherwise nontoxic prodrugs, might allow deletion of engrafted cells in the event of an adverse effect such as graft-versus-host disease or the induction of a neoplasm. In addition, expression of a prodrug activator in tumour-infiltrating haematopoietic cells could provide a means of specifically activating a cytotoxic agent within a tumour mass.

Type
Review Article
Copyright
© Cambridge University Press 2004