Prostate cancer - CG7870
One of the commonest forms of cancer in men, prostate cancer is increasing in incidence as the population ages.
One of the commonest forms of cancer in men, prostate cancer is increasing in incidence as the population ages.
The prostate gland's luminal cells produce prostate-specific antigen (PSA), and it is thought that elevated levels are characteristic of cancerous prostate cells. PSA can be detected in the blood, and high levels are commonly seen in prostate cancer patients, so it is a very useful disease marker.
Androgens, including testosterone, are responsible for regulating the expression of PSA. They bind to the androgen receptor, which is necessary for the formation of both normal prostate cells and early-stage cancerous ones. Removing the androgens can thus be an effective treatment for the first couple of years. After this time, in most patients the cancer becomes androgen independent, so hormone treatment is ineffective. Once the cancer has reached a hormone refractory stage, treatment options are currently limited.
A new strategy is being investigated by Cell Genesys. It involves the transcriptional targeting of transgene expression. The transgene is transcribed only in cells that contain a specific promotor, which is active in the cancer cells but silent in normal ones. The company is using recombinant adenoviruses to develop oncolytic viruses against prostate cancer, and is pursuing CG7870, a selective replication-competent adenovirus.
In a Phase I/II trial, 20 patients with locally recurrent prostate cancer and rising PSA levels were given the virus in one of three different doses, administered directly to the prostate under spinal anaesthesia using a brachytherapy template and ultrasound 3D imaging.1 The treatment was well tolerated, no serious adverse events were seen, and the most common side effects were local reactions at the injection sites and flu-like symptoms.
After six months, three-quarters of the evaluable patients remained progression free, and all those given the highest dose saw their PSA levels decline. Although none of the patients had a complete or partial response, the trial showed the strategy is feasible.
A second Phase I/II trial was carried out, with the virus administered at various dose levels intravenously to 23 patients with hormone refractory metastatic prostate cancer.2 It was well tolerated at all the different doses, and again flu-like symptoms represented the major side-effect. PSA levels stabilised in six of the patients. Trials continue, with the virus being administered by injection directly into the prostate, in combination with radiotherapy.