Genetic manipulation of drug sensitivity in haematopoietic cells.
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.
Southgate
Thomas
T
Cancer Research UK Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK. tsouthgate@picr.man.ac.uk
Fairbairn
Leslie J
LJ
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019450:Genes, MDR; D041722:Genes, Transgenic, Suicide / Q000502:physiology; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000235:genetics
D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes