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Combining gene and immunotherapy for prostate cancer

Prostate Cancer and Prostatic Diseases volume 11, pages 187–193 (2008)Cite this article

Abstract

The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in pre-clinical studies and is currently being assessed in phase I and II clinical trials in prostate cancer. Enhanced cell killing by apparent immune-mediated mechanisms has been shown in pancreatic and colorectal cancer models, by co-expressing murine granulocyte macrophage colony-stimulating factor (GM-CSF) with NR in a single replication deficient adenoviral vector. This consists of the CMV immediate early promotor driving expression of NR, with an internal ribosome entry site (IRES) and the gene for murine GM-CSF (mGM-CSF). To examine if similar enhancement of tumour cell killing could be produced in prostate cancer, the TRAMP model was chosen. Results illustrate that the combination of suicide gene therapy using NR and CB1954, with cytokine stimulation with mGM-CSF gives an improved response compared with either modality alone. The mechanism of this improved response is however likely to be non-immune based as it lacks a memory effect.

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Acknowledgements

This work was supported by the Medical Research Council, UK. We also thank Dr Chris McConkey of the University of Birmingham Clinical Trials Unit for statistical analysis of survival data.

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Author notes

  1. N K Green & N D James

    Present address: 2Current address: Hybrid systems Ltd, Oxford BioBusiness Centre, Littlemore Park Littlemore, Oxford, OX4 4SS, UK.,

Authors and Affiliations

  1. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK,

    J G Young, N K Green, V Mautner, P F Searle, L S Young & N D James

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Correspondence to N D James.

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Young, J., Green, N., Mautner, V. et al. Combining gene and immunotherapy for prostate cancer. Prostate Cancer Prostatic Dis 11, 187–193 (2008). https://doi.org/10.1038/sj.pcan.4501008

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