Promising antibody therapy reduces tumor growth and increases survival of pancreatic cancer mice

Scientists have found a way to target and eliminate a single protein that, according to their knowledge, is largely implicated in the growth, survival, and invasion of pancreatic cancer cells.

Called αvβ6, the protein is present on the surface of more than 80% of pancreatic ductal adenocarcinoma (PDAC) – the most common form of pancreatic cancer – and is essential for accelerating the growth and spread of tumor cells.

In a new study, published today in the Journal of Pathology, a team of researchers from the Barts Cancer Institute, Queen Mary University in London, was able to confirm the prevalence of αvβ6 not only in the primary cancer, but also in the metastasized tumors that had spread from the pancreas to other organs of the body.

The study shows how a particular antibody, used in combination with gemcitabine, a flagship pancreatic cancer drug, has successfully reduced tumor growth in mice and multiplied by six the survival time compared to control.

The team says its findings confirm that αvβ6 should be at the center of research on new antibody therapies for pancreatic cancer.

The study, funded by the Pancreatic Cancer Research Fund, was led by Professor John Marshall. The University of Nebraska's rapid autopsy program, which provided researchers with access to tissue samples from metastatic tumors and primary tumors, was key to its success.

"The badysis of these samples provided much richer data than in previous studies," says Professor Marshall. "Previously, we only looked at surgically removed tumor specimens that, by definition, were not as advanced.With the rapid autopsy program samples, we were able to confirm the αvβ6 the protein is retained when the cancer spreads and confirms its importance. "

The team then developed PDAC tumors containing the αvβ6 proteins that were introduced into mice and treated with a specific antibody called 264RAD, developed by the team in partnership with the biopharmaceutical company AstraZeneca.

Using a mouse strain whose tumors closely mimic the human form of the disease, the team has shown that it can increase mouse survival by an average of 10 days to 60 days using a combination of 264RAD and gemcitabine.

In particular, the researchers found that the number of blood vessels in the tumor had decreased, as had the number of fibroblasts – a type of cell that contributes to the formation of tissue structure, including tumors, and which also plays a role. essential role in the injury. healing. The tumor produces blood vessels and fibroblasts via a cellular signaling protein called TGFβ – a protein normally activated by the body as part of the wound healing process.

Based on these findings, the team hypothesized that the protein αvβ6 is responsible for the continuous activation of TGFβ and the production of blood vessels and fibroblasts to promote tumor growth.

Professor Marshall says:

When you cut yourself and the wound heals, it's the same αvβ6 activation of TGFβ which requires blood vessels and fibroblasts to heal the wound. Cancer cells reuse these same skills from αvβ6 to use himself.

A scientist, Harold Dvorak of Harvard Medical School, described cancer as a "healing wound." Even though he did not know it, he could have talked about αvβ6. So, targeting αvβ6we also reduce TGFβ, which slows the development of cancer. "