Open Access

Genetically modified macrophages expressing hypoxia regulated cytochrome P450 and P450 reductase for the treatment of cancer

  • Authors:
    • On Kan
    • Debbie Day
    • Sharifah Iqball
    • Frances Burke
    • Matthew J. Grimshaw
    • Stuart Naylor
    • Katie Binley
  • View Affiliations

  • Published online on: December 15, 2010     https://doi.org/10.3892/ijmm.2010.583
  • Pages: 173-180
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Abstract

This study describes a combined gene and cell therapy based on the genetic modification of primary human macrophages, as a treatment for cancer. Here, we have utilised the tumour-infiltrating properties of macrophages as vehicles to deliver a gene encoding a prodrug-activating enzyme such as human cytochrome P450 2B6 (CYP2B6) inside tumours followed by killing the tumour cells with the prodrug cyclophosphamide (CPA). Macrophages were transduced with an adenoviral vector that expresses human cytochrome CYP2B6 via a synthetic hypoxia responsive promoter (OBHRE) and with human P450 reductase (P450R), via the CMV promoter. In the presence of CPA, these genetically modified macrophages showed increased cytotoxicity against various tumour cell lines compared to untransduced macrophages or macrophages transduced with CYP2B6 alone. In human ovarian carcinoma xenograft models, the median survival of mice treated with genetically modified macophages plus CPA increased up to two-fold compared to the survival of mice treated with untransduced macrophages and CPA. Genetically modified autologous macrophages may be a feasible therapeutic option for the treatment of some solid tumours, such as ovarian cancer.

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February 2011
Volume 27 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kan O, Day D, Iqball S, Burke F, Grimshaw MJ, Naylor S and Binley K: Genetically modified macrophages expressing hypoxia regulated cytochrome P450 and P450 reductase for the treatment of cancer. Int J Mol Med 27: 173-180, 2011
APA
Kan, O., Day, D., Iqball, S., Burke, F., Grimshaw, M.J., Naylor, S., & Binley, K. (2011). Genetically modified macrophages expressing hypoxia regulated cytochrome P450 and P450 reductase for the treatment of cancer. International Journal of Molecular Medicine, 27, 173-180. https://doi.org/10.3892/ijmm.2010.583
MLA
Kan, O., Day, D., Iqball, S., Burke, F., Grimshaw, M. J., Naylor, S., Binley, K."Genetically modified macrophages expressing hypoxia regulated cytochrome P450 and P450 reductase for the treatment of cancer". International Journal of Molecular Medicine 27.2 (2011): 173-180.
Chicago
Kan, O., Day, D., Iqball, S., Burke, F., Grimshaw, M. J., Naylor, S., Binley, K."Genetically modified macrophages expressing hypoxia regulated cytochrome P450 and P450 reductase for the treatment of cancer". International Journal of Molecular Medicine 27, no. 2 (2011): 173-180. https://doi.org/10.3892/ijmm.2010.583