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Foot-and-mouth-disease virus could help target pancreatic cancer

12 February 2020

A PCRF-funded project is using the foot-and-mouth-disease virus to help tackle pancreatic cancer.

Researchers at Queen Mary University of London have identified a peptide, or protein fragment, taken from the foot-and-mouth-disease virus that targets another protein, called avβ6 (alpha-v-beta-6). This protein is found at high levels on the surface of the majority of pancreatic cancer cells.

Working jointly with Spirogen (now part of AstraZeneca) and ADC Therapeutics, the team have used the peptide to carry a highly potent drug, called tesirine, to the pancreatic cancer cells. When mice with pancreatic cancer tumours were treated with the drug and peptide combination, the tumours were completely killed.

Professor John Marshall, Queen Mary University of LondonLead researcher Professor John Marshall, from the Cancer Research UK Barts Centre, explains: “Foot-and-mouth-disease virus uses avβ6 as a route to infect cattle, as the virus binds to this protein on a cow’s tongue. By testing pieces of the protein in the virus that attaches to avβ6, we’ve developed a route to deliver a drug specifically to pancreatic cancers. Our previous research had shown that 84 per cent of pancreatic cancer patients have high levels of avβ6 on their cancers.”   

The team performed tests of the peptide/tesirine combination in both cells in the laboratory and in mice. They used genetically identical human cancer cells, some that had avβ6 on their surface and some that had no avβ6. Both types of cells were exposed to the peptide and drug combination. The cells with avβ6 were most affected, while the avβ6 negative cells needed much higher doses of the drug for the cells to be killed.

The tests in mice gave the most impressive results. Mice that had avβ6-positive tumours were given a tiny dose of the peptide-drug combination three times a week, and this stopped the tumours growing completely. But when the dose was increased and given just twice a week, all tumours in mice that were avβ6 positive were completely killed.

“These very exciting results, that are the result of many years of laboratory testing, offer a completely new way of treating pancreatic cancer.” says Professor Marshall. “One advantage of targeting avβ6 is that it is very specific to the cancer, because most normal human tissues have little or none of this protein. So we’re hopeful that, if we can develop this into an effective treatment for pancreatic cancer, it would have limited side effects.”

The team now plan to further test the peptide and drug combination in more complex mice models, to determine if it can also impact on pancreatic cancer metastases, before moving to clinical trials.

The study is published in the journal,Theranostics. 

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