AdUP clinical trial of prodrug activation gene therapy with GM-CSF
(Searle, in collaboration with Patel, Viney, James, Porfiri)
The replication-defective adenovirus AdNRGM encodes both nitroreductase (prodrug-activating enzyme) and GM-CSF, for immune stimulation. We plan to test this by template-guided injection into the prostates of men with locally recurrent, hormone refractory prostate cancer, with subsequent administration of the prodrug CB1954. We will monitor the levels of the tumour marker PSA in the blood for up to a year following treatment, and monitor the induction of tumour-specific immune responses.
Investigation of CD40L for gene therapy of liver cancer
(Searle, in collaboration with Simon Afford [Centre for Liver Research, Infection & Immunity])
CD40L is a potent immunostimulatory ligand capable of maturing dendritic cells and licensing them for activation of cytotoxic T cells. It also exhibits direct pro-apoptotic activity in a number of tumours. In this project we will investigate the potential
for CD40L gene therapy of liver cancer, including evaluation of oncolytic adenovirus vectors that are able to replicate selectively in cancer cells, thus contributing to tumour-destruction while promoting immune attack of the cancer.