The discovery of a “virus that 'kills off' prostate cancer cells” has been described in the Daily Mail. It reported that scientists injected six prostate cancer patients with a ‘tame’ virus and found it killed cancer cells while sparing healthy tissue.
The research article reports both pre-clinical studies on cancer cells and mice in the laboratory as well as an early clinical trial in six patients with advanced prostate cancer. The virus was injected into their cancers three weeks before their prostates were due to be removed. The infected cancer cells showed evidence of cell death and there were signs of an immune system response and cell changes, suggesting that the virus could be an effective cancer treatment.
This is an early report of a new type of treatment for prostate cancer. Based on these results, the researchers hope to go on to the first stage of full trials of the viral treatment in more people with advanced prostate cancer. These trials will go some way to indicating how useful this treatment might be, compared with existing treatments for prostate cancer.
Where did the story come from?
The research was carried out by Dr Chandini M. Thirukkumaran and colleagues from the University of Calgary and other institutions in Canada. The study was supported by grants from the Prostate Cancer Research Foundation of Canada, the National Cancer Institute of Canada, the Canadian Cancer Society and Oncolytics Biotech, Inc. (the Canadian company developing the treatment). The paper was published in the peer-reviewed medical journal Cancer Research.
The Daily Mail correctly highlights that these are early days for the treatment and that “much larger trials are needed to make sure it works, and even then it would take a decade for the treatment to be widely available”.
What kind of research was this?
The journal article reports on several studies in cells, animals and humans that all focussed on a new viral treatment for cancer. The treatment is based on a ‘reovirus’ (short for respiratory, enteric, orphan virus). This virus is common and usually causes very minor flu symptoms, and often no symptoms at all, in humans. The virus appears to kill cancerous cells over healthy cells. It has already been shown to have potential for treating other cancers such as bowel, colon, ovarian, breast, and bladder cancer.
What did the research involve?
The aim of this research was to provide the necessary preclinical data for a full phase I clinical trial of a treatment utilising the virus in men with advanced prostate cancer.
The researchers report on three studies, each at a different stage of the process towards developing a treatment. In the first study, normal human prostate cells and prostate cancer cells grown in the laboratory were exposed to either dead or live reovirus, to see what effect it had. The researchers also tested how much virus the infected cells were producing up to 72 hours after infection. The second study involved injecting human prostate cancer cells into the hind legs of mice. The researchers then measured the growth of any tumours that developed and took various cellular measures of cancer behaviour, both with and without the injection of the virus.
For the clinical parts of the study, six patients were recruited from local prostate cancer referral clinics in Calgary, Canada. All six had advanced cancer confined to the prostate gland, which means that the study was not testing the treatment for prostate cancer that had spread beyond the prostate gland. The patients had been given a biopsy confirming prostate cancer, and were booked for surgery called radical prostatectomy, in which the whole of their prostate would be removed. They were otherwise healthy and not taking any drugs to suppress their immune system.
Patients were then treated with the reovirus by injection. The methods were said to have been developed in a previous phase I study. Guided by an ultrasound probe, 1 mL of the virus solution was injected directly into an identified cancerous region and a metal marker left at the injection site so that the cells nearest to the injection could later be identified for analysis after the prostatectomy.
Patients were then tested weekly for three weeks for signs of toxicity and evidence of viral shedding (or spread) in the urine, faeces and blood, and monitoring of prostate-specific antigen levels (a marker of cancer activity) before their prostatectomy. The prostatectomy went ahead as planned, and the entire prostate was removed.
After the planned surgical removal of the prostate gland, the tissue was examined for signs of inflammation and cell death.
What were the basic results?
In the preclinical part of the study, the researchers found that the live reovirus was able to infect human prostate cancer cells and kill them. Human prostate cancer tumours grown in mice shrank when injected with the virus.
In the clinical part, the researchers found that the treatment was well tolerated, except for a mild flu–like illness seen in four of the six patients. Patients recovered from these symptoms within 24 hours without needing treatment.
Cancer activity, as indicated by prostate-specific antigen values, did not change greatly over the course of the study. Three patients showed signs of the virus in their urine at week one, but had negative blood tests for the virus.
There was a rise in antibodies to the virus within one week of the injection, suggesting that there had been an immune response to the new virus and that this may have limited the viruses spread to other areas of cancer in the gland.
Analysis of the prostate tissue also suggested that the reovirus did not infect healthy noncancerous tissue, possibly also inhibiting its spread to other cancerous areas. There were signs that cells near to the injection site were dying, and that immune system cells were infiltrating the area.
How did the researchers interpret the results?
The researchers say that this is the first study to provide evidence of an effect of the new reovirus
treatment for prostate cancer in both preclinical and clinical settings.
They suggest the potential value of their finding is that patients may be able to avoid some of the problems of current treatments for localised prostate carcinoma, such as erectile dysfunction,
bowel and bladder problems.
In addition, they say, “Those patients in which radical radiotherapy or radical prostatectomy are contraindicated may well be candidates for reovirus therapy.”
This is early research on a new treatment for prostate cancer. It is worth noting that:
- The virus has already been tested, and shown some success, in treatment for other cancers. This means that the route to clinical use may be shorter for this treatment indication but it will not get around the fact that many more patients will need to be tested in rigorous trials to see if the treatment is better than current alternatives.
- The treatment seemed to have very few side effects, which is a positive sign for a cancer treatment.
- The researchers acknowledge that it is unfortunate that the reovirus did not seem to infect non-cancerous tissue after the injection as this means that it is unlikely that the virus could spread to other areas of the prostate cancer and kill these, in the same patient.
Overall, this report shows another type of cancer that may respond to the reovirus treatment. More studies in many more patients will be needed to decide if the new treatment has a place and where that place might be among existing treatments for prostate cancer.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Daily Mail, 10 March 2010
Links to the science
Cancer Research 2010; Published online first March 9 2010
Cochrane Database of Systematic Reviews 2007, Issue 3
Cochrane Database of Systematic Reviews 2006, Issue 4