Nitroreductase suicide gene and immunotherapy in locally relapsed, castrate resistant prostate cancer

Viney, Richard Philip Charles (2014). Nitroreductase suicide gene and immunotherapy in locally relapsed, castrate resistant prostate cancer. University of Birmingham. Ph.D.

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Abstract

In this thesis we validate the efficacy of a new adenoviral construct in prostate cancer cell lines in preparation for a gene and immunotherapy clinical trial in prostate cancer. By demonstrating the constructs ability to infect prostate cancer cells and cause them to die with the introduction of the prodrug, CB1954 as well as releasing a biologically active cytokine, GMCSF we secured GTAC approval to proceed to a phase I/II clinical trial in patients with local relapse after treatment with curative intent for prostate cancer. A tertiary endpoint in the trial is evidence of immune responses relating to treatment. To measure this we have modified an interferon gamma ELISpot assay to measure T cell mediated immune responses. We have then used this assay on 38 patients with suspected or diagnosed prostate cancer. In this study we have found the assay to be acceptable to patients and deliverable within the setting of the clinical trial. We found evidence of strong immune responses in patients with low and intermediate risk prostate cancer based on D’Amico’s classification with these responses declining in more advanced patients. We found that some interventions lead to an increase in immune responses and these observations warrant further exploration.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):