Griffiths, L; Binley, K; Iqball, S; Kan, O; Maxwell, P; Ratcliffe, P; ... Naylor, S; + view all Griffiths, L; Binley, K; Iqball, S; Kan, O; Maxwell, P; Ratcliffe, P; Lewis, C; Harris, A; Kingsman, S; Naylor, S; - view fewer (2000) The macrophage - a novel system to deliver gene therapy to pathological hypoxia. GENE THER , 7 (3) 255 - 262.
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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.
|Title:||The macrophage - a novel system to deliver gene therapy to pathological hypoxia|
|Keywords:||macrophage, hypoxia, cytochrome P450, cyclophosphamide, gene delivery, adenovirus, PAS DOMAIN PROTEIN-1, STABLE TRANSDUCTION, IN-VIVO, TUMOR, CELLS, IMMUNOTHERAPY, ACTIVATION, EXPRESSION, RECEPTORS, ENHANCER|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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