Thursday September 1 2011
The study used a genetically engineered poxvirus
The BBC reports that an “‘anti-cancer virus’ shows promise”, and that “an engineered virus, injected into the blood, can selectively target cancer cells throughout the body”.
This news is based on research that used a genetically engineered virus that had been rendered harmless. The virus was used to infect specific tumours and produce proteins that could damage the tumour cells. Researchers injected the modified virus into the blood of 23 patients with advanced cancers and measured whether the virus was able to enter the cells, copy itself and produce the desired proteins. The virus was found to infect tumour cells, while not infecting healthy cells. Additionally, the production of desired proteins increased as the dose of virus given increased, meaning that the dose received by the tumour could potentially be controlled. The study also found that there were few serious side effects of treatment, and that patients tolerated the treatment well at high doses.
This preliminary research showed that this virus can successfully target cancer tissue and produce specific proteins in high concentrations. The researchers say that such a delivery method has never been used before, and could be a promising method of delivering high concentrations of multiple cancer therapies directly to diseased tissue. Further research, however, is needed before we will know how successful such a method will be at treating cancer.
Where did the story come from?
The study was carried out by researchers from the Billings Clinic, the Cancer Centers of the Carolinas, the University of Pennsylvania Medical Center, the biotechnology companies Jennerex and RadMD in the US; the Ottawa Hospital Research Institute, the University of Ottawa and Robarts Research Institute in Canada; and Pusan National University in South Korea. The research was funded by Jennerex Inc., the Terry Fox Foundation, the Canadian Institute for Health Research, and the Korean Ministry of Health, Welfare and Family Affairs. The study was published in the peer-reviewed journal Nature.
The media reports accurately reflected the preliminary nature of this research.
What kind of research was this?
This was a phase 1 clinical trial that investigated the effectiveness and safety of a technique that involves infecting cancer cells in humans with a virus to deliver targeted treatment. This type of study design, where all patients receive the same treatment and there is no control group, is also known as a case series.
The researchers thought that they could engineer a virus to infect cancer tissue and not healthy tissue, thereby delivering cancer therapies specifically to tumours. They chose a poxvirus for their experiments because it has been shown to be resistant to the human immune system and because it spreads quickly through the blood to distant tissues. The virus is thought to be too large to enter healthy tissue easily, but may enter tumour tissue more easily as the blood vessels supplying tumours are more “leaky”.
They also say that a form of the poxvirus has been genetically engineered so that it can only replicate (make more copies of itself) in cancer cells. This is possible because the genetically engineered virus needs specific biochemical pathways that are commonly found in many cancers but not normal tissue. The replication of this virus, called JX-594, within the cancer cells can cause them to burst and die.
The JX-594 virus has also been engineered to produce proteins that attract immune system cells to attack the cancer, and another protein that allows cells producing the protein to be easily identified. Although these were the specific proteins that the virus was engineered to produce, if this targeting technique works, the virus could potentially be engineered to produce other anti-cancer proteins.
This was a preliminary study to assess whether the basic mechanics of using this virus to deliver cancer therapies would both work and be safe. The study did not look at whether or not this method will successfully treat cancer, or whether it will be more successful than currently used treatments. Further research is needed to answer such questions.
What did the research involve?
The researchers first determined, in the laboratory, whether the virus infected cancer tissue, normal tissue or both. Once it was shown that the virus infected only the cancer tissue in seven out of ten samples, they moved on to studying the effectiveness and safety of the virus in 23 people with advanced cancer that had not responded to other treatments. The patients included in the trial had different types of cancer, including lung, colorectal, thyroid, pancreatic, ovarian and gastric cancer, as well as melanoma, leiomyosarcoma (a type of muscle tissue cancer) and mesothelioma.
The researchers injected the patients with multiple doses of the virus and assessed, using biopsies, whether the virus was delivered to the tumour and healthy tissue, whether the virus replicated itself once in either type of tissue, and whether it produced the desired proteins.
The researchers also assessed the safety of using the virus, including the maximum dose tolerated by the patients, and any side effects.
What were the basic results?
The researchers found that in 13 of the 23 people treated (56.5%) the disease remained stable or showed a partial response at four to ten weeks after the injection of the virus. Patients who received higher doses showed better responses to treatment and disease control.
They also found that new tumour growth after treatment was less frequent in those who received high doses of the virus compared with those who received low doses. The biopsies and antibody tests confirmed that the virus entered tumour cells but not healthy cells. Additionally, the tests showed that the virus replicated and produced the desired proteins in a dose related manner. This means that the higher the dose of virus given, the more replication and protein production was seen. When the healthy tissue that was located directly next to the tumours in the body was examined, the researchers found that the virus was able to infect some of the healthy tissue, but there was no evidence that the virus replicated in these cells or produced the proteins.
When examining the safety of using the virus, the researchers found that treatment with JX-594 was generally well tolerated at the high doses, and common side effects included flu-like symptoms that tended to last up to a day.
How did the researchers interpret the results?
The researchers say that this is the first study that has shown that a virus can be injected into a patient’s bloodstream and used to produce specific proteins in advanced tumour tissues. They say that the results indicate that JX-594 could be used to deliver high concentrations of multiple cancer therapies directly to cancer cells.
Researchers say that further studies are being done to examine the effect of repeated injection with JX-594. These aim to determine whether the effectiveness of JX-594 as a delivery system is diminished after the body and immune system are repeatedly exposed to the virus.
This research examined the ability of a genetically engineered virus to target specific tumour tissue with anti-cancer proteins. It was a small preliminary study in humans, which aimed to determine whether or not the delivery method was feasible, and whether it would be tolerated by patients. The results indicate that using the JX-594 virus to target cancer cells is feasible and seems to be safe in the short term. However, this method will require extensive testing in larger and longer-term trials before the benefits and risks are fully understood.
It is important to point out that the ability of the JX-594 virus to replicate and express proteins is dependent on the presence of a specific set of biochemical processes (called a pathway) within the cancer cells. Not all cancers possess this pathway, and therefore they may not all be treatable using this method.
This was a short study involving a small number of patients. Tests on the delivery and replication of the virus were conducted over 29 days, and patients were followed for about four months. While such a short study period is suitable for a phase I trial, longer trials involving more people will be needed to test the effectiveness of this virus in the treatment of cancer.
The researchers say that another potential benefit of this delivery system is that the virus could be used to deliver multiple cancer therapies to tumours, allowing for higher concentrations of these therapies in cancer tissue compared with healthy tissue. They say that the virus could also be engineered in such a way to enable blood tests to monitor how the treatment was working.
It is important to remember that this study is at the first stage of human testing. At this stage these tests are not specifically aimed at examining the effectiveness of the method to treat cancer, but at testing whether the virus worked as a delivery system for treatment and was safe. The delivery of cancer therapies directly to tumour tissue in this way could be an important step in treating cancer while reducing harm to healthy tissue. Further studies will be needed to determine whether this will become a reality.