Researchers Develop Faster Cancer Drug Discovery Platform

By C. Rajan, contributing writer

University of Michigan researchers have developed a new method for identifying potential cancer therapeutics that speeds up the traditionally slow drug discovery process. Using this new platform, the researchers were able to identify a novel antibody which is currently being evaluated as a potential treatment for breast, ovarian, and other cancers.

In the study led by Stephen Weiss at the U-M Life Sciences Institute, the researchers developed an approach that reproduces the natural in vivo environment of cancer cells so that drugs can be tested quickly against these cancer cells, in turn improving the odds that these drugs would work the same way against human cancer cells.

"Discovering new targets for cancer therapeutics is a long and tedious undertaking, and identifying and developing a potential drug to specifically hit that target without harming healthy cells is a daunting task," Weiss said. "Our approach allows us to identify potential therapeutics in a fraction of the time that traditional methods require."

Weiss and his team used collagen, which forms connective tissues similar to that found surrounding breast cancer cells in human patients, to create a 3-D matrix in which they embedded breast cancer cells. Thus, the cancer cells grew as they would normally in human tissue, so that when the researchers injected the cancer-collagen tissue composites into mice, the mice released thousands of antibodies directed against the human cancer cells.

The researchers then isolated these antibodies and tested their tumor fighting ability against human cancer cells.

"We create an environment in which cells cultured in the laboratory 'think' they are growing in the body and then rapidly screen large numbers of antibodies to see if any exert anti-cancer effects," Weiss said. "This allows us to select promising antibodies very quickly and then work to identify what the antibody targets on the cancer cell surface."

One of the isolated antibodies, 4C3, showed excellent anti-cancer activity and was able to completely stop proliferation of the breast cancer cells. The team also identified the target molecule on the cancer cells which the antibody binds to. The next step for them, Weiss said, would be to further engineer the antibody to generate humanized monoclonal antibodies as a potential therapeutic.

"We still need to do a lot more work to determine how effective 4C3 might be as a treatment for breast and other cancers, on its own, or in conjunction with other therapies," Weiss said. "But we have enough data to warrant further pursuit, and we are expanding our efforts to use this discovery platform to find similarly promising antibodies."

The results were published online in the Proceedings of the National Academy of Sciences.