Cancer Research UK scientists at the University of Leeds have developed a new way of modifying viruses to seek out and destroy cancer cells, according to research published in Gene Therapy today1 (Friday).
The researchers exploited the unique markers that appear on the surface of cancer cells to engineer a range of proteins that recognise and attach to these markers. These ‘re-targeting’ proteins can be added to a virus so that it recognises and infiltrates cancer cells.
The virus can then deliver genes that can make cancer cells more sensitive to drugs, introduce ‘suicide’ genes to the cancer cell or replace the missing and defective genes that caused the cancer to develop – an approach called gene therapy.
The scientists developed their system by engineering these ‘retargeting’ proteins to recognise markers on the surface of bladder cancer cells, and potentially to any kind of cancer. When tested in the lab the virus was able to recognise and enter the cancer cells with these markers. They were also able to add these retargeting proteins to an existing gene therapy virus so that it recognised and attacked these bladder cancer cells, increasing their drug sensitivity.
Gene therapy has had limited success so far, mainly because the approach to deliver such treatments have not been efficient or specific enough to only target tumour cells.
University of Leeds scientist Dr John Chester, who led the Cancer Research UK funded study, said: “Gene therapies have been out of fashion over the last couple of years. This isn’t an indication that they don’t work; just that we haven’t found the best way to use them yet. Our research points to a new method to optimise viruses for gene therapy and has so far been promising in the lab. We now need to test these gene therapies in patients to see if they are as effective treating cancer as our research suggests.”
They propose a number of possible uses for their system. In the first approach, a re-targeting protein that recognises a range of tumours could be combined with an existing gene therapy virus.
Another approach involves tailoring the targeting proteins to an individual patient. By examining the markers on a patient’s tumour it would be possible to add a re-targeting protein designed specifically for their cancer to a gene therapy virus.
Dr Chester added: “We also found that we weren’t limited to using only one targeting protein for each virus. We were also able to combine the virus with two different targeting proteins so that our virus can target a range of different tumour markers. This approach could be a step forward for gene therapy, particularly as it is quicker, easier and cheaper to mix and match the targeting proteins rather than engineer a completely new gene therapy virus.”
Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “This exciting early laboratory work points to a new way of attacking cancer cells by targeting the unique markers on cancer cells. It could have real benefits for patients with treatments tailored to their cancer but we first have to test it through clinical trials.”
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1 Chester, J.D., et al Retargeted adenoviral cancer gene therapy for tumour cells over-expressing Epidermal Growth Factor Receptor or Urokinase-type Plasminogen Activator Receptor (2010) Gene Therapy