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Promising antibody therapy extends survival in mice with pancreatic cancer

Scientists at Queen Mary University of London have found a way to target and knock out a single protein that they have discovered is widely involved in pancreatic cancer cell growth, survival and invasion.

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Pancreatic cancer cells. CC BY-NC Credit: Anne Weston, Francis Crick Institute
Pancreatic cancer cells. CC BY-NC Credit: Anne Weston, Francis Crick Institute

Called avb6, the protein is present on the surface of more than 80 per cent of pancreatic ductal adenocarcinoma (PDAC) – the most common form of pancreatic cancer – and is vital to increase the successful growth and spread of the tumour cells.

In the new study, published in the Journal of Pathology, a team of researchers at Barts Cancer Institute at Queen Mary were able to confirm the prevalence of avb6 not only in primary cancer, but also in metastasised tumours that had spread from the pancreas to other organs in the body.

A six-fold increase in survival time in mice

The study reports how a particular antibody, used in combination with leading pancreatic cancer drug, gemcitabine, successfully reduced tumour growth in the mice and delivered up to a six-fold increase in survival time, compared to the control.

The team say their results confirm that avb6 should be a focus for research into new antibody therapies for pancreatic cancer. 

The study, funded by the national charity Pancreatic Cancer Research Fund, was led by Professor John Marshall. Key to its success was the University of Nebraska’s Rapid Autopsy Programme, which allowed the researcher to access tissue samples from metastasised tumours as well as from primary tumours.

“Analysing these samples gave much richer data than in previous studies,” explains Professor Marshall. “Previously we only looked at samples from tumours which had been surgically removed which, by definition, were not as far advanced. Using samples from the Rapid Autopsy Programme we were able to confirm the avb6 protein is retained when the cancer spreads and confirms its importance.”

Antibody therapy reduces blood vessels in the tumour

The team developed PDAC tumours containing the avb6 protein which were put into mice and treated with a specific antibody called 264RAD, that was developed by the team in partnership with biopharmaceutical company, AstraZeneca.

Using a strain of mouse whose tumours closely mimic the human form of the disease, the team showed that they could increase the survival of the mice from an average of 10 days to up to 60 days using a combination of 264RAD and gemcitabine.

In particular, the researchers noted that the number of blood vessels in the tumour had decreased, and so had the number of fibroblasts – a type of cell that helps produce the framework of tissue, including tumours.

More information

  • Research paper: “The integrin avb6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy” by Reader et al. Journal of Pathology. doi 10.1002/path.5320
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