Scientists create light-activated cancer drugs

Behind the Headlines

Tuesday November 8 2011

Light makes the drugs activate only around the tumour

A new type of light-activated cancer drug could target tumours and leave healthy tissue unaffected, BBC News has today reported. The broadcaster says that researchers have found a way to modify drugs so that they stick to tumours, but only become activated when hit by specific waves of light.

The news is based on a study in which researchers developed a new type of drug that combines a light-sensitive chemical with antibodies that are attracted to proteins commonly found at high levels in cancer cells. The researchers then tested two drugs of this type in cancer cells and in mice with tumours. They found that the light-sensitive antibodies could attach themselves to cancer cells and were activated by specific wavelengths of light. In mice, the technique was able to shrink tumours after one dose of light.

As BBC News reported, this early work was done in mice and it is much too early to tell if it will work safely and effectively in people with cancer. However, making more targeted cancer therapies is an important area of research and this study has made a valuable, if preliminary, contribution to the field.

 

Where did the story come from?

This American study was carried out by researchers from the National Institutes of Health and funded by the National Institutes of Health, the National Cancer Institute and the Centre for Cancer Research. It was published in the peer-reviewed medical journal, Nature Medicine.

The research was covered well by BBC News, which explained it within an appropriate context and highlighted the limitations of animal studies.

 

What kind of research was this?

This laboratory research developed and tested a new type of light-sensitive cancer drug in mice.

Many existing cancer drugs are toxic to both cancer cells and the body’s healthy cells, which has led scientists to examine the potential use of targeted therapies that will only attack cancer cells. This emerging type of treatment can in theory be achieved either by creating drugs that will only attach themselves to cancer cells or by creating drugs that can be activated only once they are in the vicinity of a tumour. The scientists tried to combine these two mechanisms to create drugs that would attach themselves to cancer cells and then be activated using beams of light directed at the tumour.

The scientists took light-sensitive chemicals that are toxic to cells once they are activated by specific wavelengths of light. The researchers said that the trouble with these types of chemicals is that they don’t target a particular cell type. This means that if they were injected into the body, normal, non-cancerous tissue could be killed too. The researchers investigated whether it was possible to attach the light-sensitive drugs to antibodies, a type of special protein the immune system uses to identify foreign bodies and threats such as bacteria and cancer cells. By combining a drug with specific antibodies, they would be able to direct it to attach to specific cells.

The researchers developed the drugs and then tested whether they could kill tumours in mice. As this was preliminary animal research, it isn’t yet clear whether this type of drug would be safe to use in humans.

 

What did the research involve?

The researchers first attached a light-sensitive chemical to antibodies that targeted a type of protein called an “epidermal growth factor”. High levels of these proteins are found on some cancer cells. The researchers then looked at how well the antibody would target the epidermal growth factors once it had the light-sensitive chemical attached.

The researchers made two drugs that used antibodies that target epidermal growth factor receptors: one that targeted the HER1 receptor and another that targeted HER2, a protein already found to play a role in some aggressive breast cancers. The drug Herceptin works by targeting HER2.

The researchers then looked at how well their drugs would kill lab-grown cells that were genetically modified to produce lots of HER2 or lots of HER1. They put the drugs on the cells, stimulated them with light from a fluorescence microscope and counted the number of dead cells.

The researchers then investigated how well the drugs would target tumours that were growing on the back of mice and whether they would cause these tumours to shrink. The mice had some tumours that were HER1-positive and some that were HER2-positive. The mice were injected with the drugs and the tumours were exposed to near-infrared light one day later.

 

What were the basic results?

The researchers found that attaching the light-sensitive chemical to the antibody did not interfere with its ability to bind to the epidermal growth factor receptor.

They showed that both drugs could kill cells grown in a lab after one hour of the treatment.

They found that the drugs had attached to the tumour tissues in mice and tumour shrinkage was confirmed by day seven after injecting the drug and six days following the light stimulation.

 

How did the researchers interpret the results?

The researchers said that they had developed a target-specific “photoimmunotherapy”, in other words, a therapy using both light and features of the immune system. They said that the wavelengths of light needed to activate the drugs were able to penetrate into tumours under the skin and shrink the tumours after a single dose.

The researchers also said that it should be possible to attach the light-sensitive chemical to different antibodies and that this technique may be useful in diagnosing cancers, as it would be possible to detect the fluorescence of the antibodies when attached to tumours in the body.

 

Conclusion

While the current generation of chemotherapy drugs can be extremely powerful for fighting cancer, their power means many also carry the risk of causing side effects and damaging healthy body tissue. This new “proof of principle” animal research has identified a method that might be able to confine the toxic effects of future chemotherapy drugs to cancer cells, thereby limiting the harmful effects they can have on the rest of the body.

To achieve this result, the scientists took the novel approach of attaching light-sensitive chemicals to antibodies that target proteins often found in high levels on cancer cells. Effectively, this method combined targeted delivery of drugs with targeted activation using light, which resulted in the death of the cancerous cells that they were attached to.

However, while this marks the technique out as one for future exploration, this was animal research and therefore its results cannot guarantee that the drugs would be an effective and safe treatment for humans. In particular, the technique was used in mice to treat tumours close to the surface of the body; further research is needed to see if this technique works for tumours in other locations and in human proportions. Nevertheless, developing targeted cancer treatments is a hot area of research and this study is likely to have made a valuable contribution to this field.

Links to the headlines

Light 'promising' in cancer fight. BBC News, November 8 2011

Links to the science

Mitsunaga M, Ogawa M, Kosaka N et al. Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nature Medicine, November 6 2011

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Edited by NHS Choices