Monday June 20 2011
Prostate cancer cells
BBC News has reported that a vaccine offers hope for prostate cancer sufferers. The broadcaster reported on a new approach to developing cancer vaccines in which “DNA from healthy cells was used to create a vaccine which cured 80% of mice”.
During the research, scientists genetically engineered a virus so that it would contain a library of DNA from a normal human prostate. They found that when they injected this virus into mice that had prostate tumours, the mice’s immune system recognised the prostate tumour and cured the tumours in 80% of cases. They found that a virus containing a human prostate DNA library was better at curing the tumours than a virus containing mouse prostate DNA. The virus, when injected into the bloodstream, did not kill normal non-cancerous prostate cells in mice.
This research has in effect produced a vaccine that could target the immune response to prostate tumours in mice without having to identify the specific proteins on the surface of tumour cells, which would be necessary to make conventional vaccines. The research is preliminary and, as it was carried out in mice, further research is needed to see whether this approach could be used safely and effectively in humans. It is far too early to suggest that this experimental study offers hope for a vaccine against prostate cancer or any other cancer.
Where did the story come from?
The study was carried out by researchers from the Mayo Clinic in the USA, the Cancer Research UK Clinical Centre in Leeds, the University of Surrey and the Institute of Cancer Research, London. It was funded by The Richard M. Schulze Family Foundation, the Mayo Foundation, Cancer Research UK, the US National Institutes of Health and a grant from the Terry and Judith Paul charitable body.
The study was published in the peer-reviewed journal Nature Medicine.
BBC News summarised this complex research well. The coverage in the Daily Mirror and Daily Mail of this preliminary animal research was overly optimistic. In particular, the Mirror’s statement that “cancer vaccines could become the next generation of therapy after a new method of treatment was discovered” does not reflect the findings and implications of this early-stage research.
What kind of research was this?
This experimental research in cell cultures and animals aimed to develop a vaccine that could induce an immune response to tumour cells but spare normal healthy tissue.
The researchers said that therapies harnessing the immune system (immunotherapies) to fight cancer have been hindered by a lack of knowledge of antigens that are specific to tumours and not found on normal tissue. Antigens are proteins or chemicals that are recognised by the body’s immune system as foreign, triggering an immune response.
The researchers’ theory was that if they took a library of DNA from healthy prostate tissue and inserted it into a virus that caused the body to mount an immune response, then the DNA would code for a variety of potential prostate-specific antigens. The virus itself would cause an immune response and as the virus contained DNA from prostate cells the immune system would see prostate cells (including prostate tumour cells) as foreign and target them too. This would mean that they could target the immune response to prostate cells without having to inject the virus directly into the prostate.
A potential problem with this approach is that as the body would attack normal healthy prostate tissue (known as an autoimmune response). The researchers investigated whether they could treat mice with this virus after they had been induced to have prostate tumours and whether the mice were spared from autoimmune attack of normal tissue if the virus was injected into the bloodstream, rather than directly into the tumour.
What did the research involve?
The researchers used genetic engineering techniques to create a library of DNA from normal human prostate cells and inserted it into a virus, called the vesicular stomatitis virus (VSV). To see whether the virus would enter cells and become active, the researchers infected a cell line (derived from hamster kidney cells) with their virus and looked at whether the prostate genes they had inserted became active. They also looked at how much virus they needed to add to the cells to produce detectable prostate gene activity.
The researchers then injected the virus into either the prostates of mice or intravenously into the bloodstream of mice, to see whether this would cause immune responses. They were particularly interested in whether there were autoimmune responses (where the body’s immune system starts to attack itself).
The researchers then injected these mice with prostate tumour cells to induce the formation of prostate tumours. They also injected another group of mice with skin cancer tumour cells to see whether any effects of the virus were specific to prostate tumour cells.
They then looked at the immune response when injecting the virus into the tumour compared to injecting the virus into the bloodstream and whether the treatment could cure the prostate tumours in the mice.
What were the basic results?
The researchers injected the prostates of mice with either the virus containing the prostate DNA or a saline solution, as a control. They found that, compared to the control injection, the virus caused enlargement of the prostate after two days but lowered the weight of the prostate after 10 days. This treatment also caused a white blood cell immune response in the mice. The researchers looked at the effect of injecting the virus into the bloodstream of the mice. They found that, in contrast to injecting the prostate with the virus, after 60 days the prostate was the same size as in the controls. The researchers said this showed that the treatment had not caused autoimmune responses.
The researchers injected the mice with prostate tumour cells to induce the growth of prostate tumours. They found that mice that had the virus injected into their bloodstream after the tumours were established produced a type of immune cell called a T helper 17 cell. These mice had increased survival, and the injections cured the tumours more effectively compared to injecting the virus directly into the tumour. Nine intravenous injections of the virus cured over 80% of mice with prostate tumours. The virus that contained prostate-specific DNA did not have an effect against other types of tumour, such as skin tumours.
After testing mice that had been injected with a virus containing a human prostate DNA library, the researchers looked at whether a virus containing a mouse prostate DNA library would give similar protection against prostate tumours. Although the virus containing the mice DNA offered some protection against tumours, the virus containing human DNA offered better protection.
How did the researchers interpret the results?
The researchers said that their research showed it was possible to vaccinate mice against existing tumours using a wide variety of antigens coded for by a library of DNA, delivered within a virus that stimulates an immune response. The introduction of this DNA library potentially allows the body to select antigens that could be tumour-specific.
The researchers say that “virus-expressed DNA libraries” from normal tissues of either humans or animal origins can be readily constructed for off-the-shelf use, and can be easily delivered into cells to potentially protect against prostate tumours.
This animal study used an interesting approach to develop a vaccine which primed the body to target prostate tumours without the need to identify prostate-specific antigens.
As this was an animal study, further research will be needed to see if this technique could be used in humans. One finding was that the vaccine worked better if the mice were injected with a virus containing a DNA library from the human prostate rather than the mouse prostate. Research would be needed to see what type of DNA would prime the best response to prostate tumours in humans.
In the study, the researchers found that the virus did not lead to an autoimmune response in the mice. However, further research would be necessary to see whether it could be safe to use in humans as there may be differences in the immune systems of mice and humans.