Combining gene and immunotherapy for prostate cancer

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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.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Prostate Cancer and Prostatic Diseases
Publisher: Nature Publishing Group
ISSN: 1365-7852
Official Date: 28 August 2008
Dates:
Date
Event
28 August 2008
Published
Volume: Vol.11
Number: No.2
Page Range: pp. 187-193
DOI: 10.1038/sj.pcan.4501008
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
URI: https://wrap.warwick.ac.uk/51876/

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