New 'multi-cancer drug' still some way off

Behind the Headlines

Tuesday March 27 2012

Anti-CD47 slowed or stopped certain cancers, but only in a lab

Scientists have developed “a drug that helps the immune system to break down cancerous tumours”, the Daily Mail has reported. The newspaper says it could help fight at least seven cancers, including breast, bowel and brain cancer.

This news is based on laboratory and animal research focused on the role of a protein called CD47, which is found on the surface of healthy cells within the body. The protein tells the immune system not to attack and 'eat' healthy cells. Recent studies have found that certain leukaemia and lymphoma cancer cells also carry this protein, which masks them from the immune system. In this new study the researchers looked at whether various other types of cancer tissue also carry CD47. They also looked at whether using a drug that blocks CD47, known as anti-CD47, could help the immune system detect and kill cancerous cells.

They found that, in initial test tube studies, anti-CD47 allowed immune cells to attack cancerous cells they would have otherwise ignored. When human tumour tissue was then implanted into mice with weakened immune systems treatment with anti-CD47 shrank the tumours and prevented them spreading to the rest of the body.

While these are certainly interesting results, they are extremely early ones produced in the artificial setting of a lab. Therefore, the research should be seen as only the first step towards developing a treatment, as we cannot yet tell whether anti-CD47 will be safe or effective in humans.

 

Where did the story come from?

The study was carried out by researchers from Stanford University Medical Center and other institutions in the US, Norway and Switzerland. Funding was provided by various charitable research funds, as well as the US National Cancer Institute, US Department of Defense and other anonymous donors.

The study was published in the peer-reviewed scientific journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

The research was covered by the Daily Mail and various international news sites, which were generally overly optimistic given the early stage of this research. So far, this area of research has only been conducted in cells in the laboratory and in mice that were transplanted with tumours. Although these experimental tests did produce promising findings, it is far too early to declare that scientists have found a miracle drug that could cure a wide range of cancers.

 

What kind of research was this?

This was laboratory and animal research that aimed to investigate the role of a protein called CD47 in solid tumours. This protein has a number of roles, one of which is to act as a 'do not eat me' signal for healthy tissues, which use the protein to prevent themselves being destroyed by the immune system.

As well as being found on healthy cells, some previous research has discovered that CD47 can be present on the surface of leukaemia and lymphoma cells (blood cancers). This has led researchers to investigate whether CD47 might also be the method by which solid tumour cells evade the immune system. Given this possibility, the researchers conducting this current study took cells from various solid cancers and tested for the presence of CD47. They also tested whether an antibody (anti-CD47) that blocked the protein would allow the cancer cells to be destroyed by the immune system.

This type of research is an essential first step in the development of potential new treatments for human cancers.

 

What did the research involve?

The researchers first looked at whether cells from various solid human tumours had CD47 on their surface, and whether the levels were higher than in cells from healthy tissue.

The researchers then conducted experiments using the anti-CD47 antibody on cells in the laboratory. First, they examined what happened when they placed tumour cells in petri dishes with anti-CD47 and macrophages. Macrophages are immune cells that engulf and destroy other cells, which is sometimes described as 'eating them'. They trialled this with cells from the various different tumour types that possessed CD47 protein.

Following their laboratory findings the researchers conducted further investigations where they transplanted human tumour tissue into mice with weakened immune systems. They aimed to see what effect anti-CD47 had on tumour growth and spread in these mice, as well as their overall survival. Again, they tested various human tumours, including transplanting ovarian cancer tissue into the abdominal cavity, breast cancer tissue into the mammary fat pads and brain cancer tissue into the mouse brain.

As a final part of their mouse experiments they tested the effects of giving anti-CD47 at a lower dose to mice with a normal immune system that were transplanted with breast cancer tissue. This was mainly to look at the potential side effects of using CD47 as a drug.

 

What were the basic results?

The researchers found that CD47 protein was present in all the solid tumours that they tested and nearly all the cells within each type of tissue – breast, colon, prostate, ovarian, bladder and liver cancers and a certain brain cancer (glioblastoma). They found that CD47 tended to be found at higher levels on cancerous cells than on cells from healthy tissues.

In their laboratory experiment the researchers demonstrated that anti-CD47, which blocks the CD47 protein, allowed the macrophages to engulf and destroy the tumour cells. The macrophages had not been able to do this in tests without anti-CD47 present.

When tumour tissue was transplanted into the mice the researchers found that administering anti-CD47 had several effects. For some larger tumours it prevented both their growth and spread to other parts of the body (metastasis). In other cases anti-CD47 prevented tumours growing from transplanted tumour cells, suggesting that the treatment potentially 'cured' the mice altogether. The treatment also prolonged the survival of the mice in at least one of the experiments. For some transplanted tumour samples, however, anti-CD47 did not affect tumour growth.

In the mice with a normal immune system, they observed that giving the antibodies did reduce tumour growth, but also led to short-term anaemia in the mice (low red blood cell count).

 

How did the researchers interpret the results?

The researchers conclude that CD47 is a molecule that is commonly found on the types of cancer cells they tested, and that it functions to block the cancer cells from being engulfed and destroyed by cells of the immune system. Blocking the function of CD47 with an antibody allows the cancer cell to be destroyed by the immune system, causing the researchers to suggest that “CD47 is a validated target for cancer therapies”.

 

Conclusion

This is valuable scientific research that furthers our understanding of how cancer cells in the body may use the CD47 protein to prevent themselves from being targeted and destroyed by the immune system. Also, the research was able to show that using an antibody that targets and blocks the protein may reduce the growth and spread of a number of different human tumours transplanted into mice. Therefore, this antibody seems to have potential as a possible cancer treatment.

However, it must be remembered that this is very early stage research and that, so far, these results have only been demonstrated in cells in the laboratory and in human cancers transplanted into mice, mostly with weakened immune systems. This means it is not known what the effects would be if anti-CD47 was given to humans who had developed cancer.

As cancer researcher Tyler Jacks of the Massachusetts Institute of Technology in Cambridge is quoted as saying in an editorial in the magazine Science, “the microenvironment of a real tumour is quite a bit more complicated than the microenvironment of a transplanted tumour, and it’s possible that a real tumour has additional immune suppressing effects”.

Another factor needing examination relates to the fact that healthy cells produce the CD47 protein. It is not known as yet what effect the antibody would have on healthy human tissues. As this animal research demonstrated, the antibody did seem to cause depletion in blood count in mice. This would be a significant adverse effect in humans with cancer, and the implications of such safety effects would have to be considered before this treatment could proceed to human testing.

Overall, much more research is needed before it will be known whether this treatment could truly offer the potential to shrink or halt the progression of human cancers.

Analysis by Bazian

Links to the headlines

Hope of fresh treatment for seven cancers after single antibody is found to shrink tumours from all of them. Daily Mail, March 27 2012

Links to the science

Willingham SB, Volkmer J-P, Gentles AJ.  The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. PNAS, published online before print March 26, 2012

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Analysis by Bazian

Edited by NHS Choices