“A common anti-diabetes drug may boost the potency of vaccines against cancer,” BBC News reported. It said that researchers gave metformin, a drug used to control blood sugar in humans, to mice that had also been given an experimental cancer vaccine. The researchers found that metformin increased the number of one type of immune system cell, the T-cell, which improved the effectiveness of the cancer vaccine.
Dr Kat Arney, Cancer Research UK's senior science information officer, said this research shows promise. New treatments are often discovered in animal research, but more work will be needed to first find a cancer vaccine that works against human cancer cells, and then to find out if this drug is effective at boosting the immune response in humans.
Where did the story come from?
The research was carried out by Dr Erika L Pearce and colleagues from the University of Pennsylvania School of Medicine and McGill University. The study was supported in part by grants from the National Institutes of Health. The study was described in a letter to the science journal Nature .
What kind of scientific study was this?
One of the aims of this animal study was to investigate how metformin, a drug used to treat type 2 diabetes, might affect the immune systems of mice that were engineered to have compromised immune systems.
The researchers explained that immune cells known as CD8 T-cells have an important role in fighting infection and can also kill cancer cells. There are several different types of these T-cells. The researchers were interested in learning more about two of these: antigen-specific effector (TE) type cells and long-lived memory (TM) cells. Following a bacterial infection, for example, the immune system produces TE cells to fight off the infection. As the bacteria are destroyed, the numbers of these TE cells decrease. The TM cells develop the ability to recognise this same infection. TM cells persist for longer and are involved in longer-term immunity. The researchers specifically wanted to know how the numbers and function of TE cells are related to TM cells. They say that these cells have a predictable response to foreign proteins, such as multiplying when they come into contact with viruses or the antigens on the surface of cancer cells. Much is already known about how these immune reactions occur but the underlying mechanisms controlling the transition to long-lived memory cells is unknown.
The researchers chose to use specially bred mice that produce TE cells when exposed to foreign proteins, but which cannot generate the TM cells needed for longer-term immunity. This meant that their immune systems could fight off an initial infection, but if they were exposed to the same source of infection at a later date, their bodies would be unable to use TM cells to quickly develop more white cells to fight off the same infection for a second time.
The metabolism of the deficient T-cells was tested using a technique that assessed the metabolism of fats, so that the researchers could further identify the pathways affected by the deficiency. They then re-tested the cells and counted the number of TM cells in other mice after they had been given the drug metformin. Metformin is a drug commonly used to treat diabetes. It works by suppressing the production of glucose in the liver. The researchers chose this particular drug because it activates a liver enzyme (AMP-activated protein kinase) that was also defective in the genetically engineered mice.
What were the results of the study?
The researchers found that, when exposed to infection, the genetically engineered mice had increased numbers of TE cells but did not generate TM cells. The researchers say this is proven by the absence of TM cells in the weeks following immunisation.
The genetically engineered mice with deficient CD8 T-cells had altered fatty acid metabolism and when their T-cells were tested they were not able to metabolise fats in the usual way. Giving the mice metformin restored this ability and also increased the numbers of TM cells they produced.
Metformin also increased the TM cells in wild-type (normal) mice, and consequently was able to considerably improve the efficacy of an experimental anti-cancer vaccine.
What interpretations did the researchers draw from these results?
The researchers say that while investigating TM cell development they made the surprising finding that energy metabolism can be “pharmacologically manipulated during an immune response to promote CD8 TM cell generation and protective immunity.”
This, they say, may have important implications for therapeutic and prophylactic (preventive) vaccine development.
What does the NHS Knowledge Service make of this study?
Animal studies are often an area of research where new (and in this case surprising) discoveries are made. By sharing their results in this way, the researchers will allow others to repeat and develop their work further. It is worth noting that:
- This is an animal study, so if this is to be developed into a method of stimulating immune responses in humans, studies in humans will be needed.
- The cancer vaccines referred to by the researchers and news sources are themselves in development and are not yet routinely available for humans.
- The possibility that metformin could help routine vaccines work better is currently speculation and was not tested by this research.
Overall, this research has been responsibly reported and will be of interest to those in the scientific community who are working hard to develop 'immunotherapy' treatments for cancer.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 4 June 2009
Links to the science
Nature, June 3 2009 (advance online publication)
Cochrane Database of Systematic Reviews 2004, Issue 3