Immune system molecules could be used to stop cancer from spreading through the body, according to new research from Queen’s University.
When cancer spreads, or metastasizes, to other organs, it is more difficult to treat, and survival is generally lower than if cancer does not spread. Researchers are testing many different strategies to stop cancer from spreading, including immunotherapy.
Cancer cells rearrange themselves and their environment
Some one-celled organisms like amoebas move around by extending a part of the cell forward, almost like a foot, with the rest of cell following. Cancer cells have their own similar version of this movement, using parts of the cell called invadopodia. Through this movement, cancer cells invade into the surrounding biological material, breaking it down and allowing cancer cells to spread throughout the body.
Cells need a molecule called MMP14 (matrix metalloproteinase 14) to form invadopodia and help them move. In fact, scientists have found that cancer cells with higher amounts of MMP14 spread more and result in lower survival than cancers that have lower amounts of MMP14.
With funding from the Canadian Cancer Society, Dr Andrew Craig and his team at Queen’s University have been studying whether blocking MMP14 could be an effective strategy to prevent cancer from spreading. They are specifically studying this strategy as a potential treatment for triple-negative breast cancer, an aggressive form of the disease that has limited treatment options and worse survival than other types of breast cancer.
Blocking MMP14 prevents cancer growth and spread
The team recently published research that looks at using immunotherapy to block MMP14. They tested a large number of immune system molecules called antibodies for their ability to bind to and block the MMP14 molecule. They found one antibody that seems to recognize MMP14 specifically and be very effective at blocking its activity.
The successful antibody attaches to MMP14 and interrupts the processes that are critical for creating a good environment for cancer cells to grow. It prevents the growth of blood vessels around tumours, disrupts the development of a low oxygen environment and improves immune system response – all of which make the biological environment around cells more hostile to cancer and limit tumour growth.
When the team tested the antibody in the lab, they found that it could block cancer growth and spread. Treatment with the antibody resulted in smaller tumours that did not grow as quickly, as well as fewer tumours that had spread.
Further research will improve effectiveness of immunotherapy
While the antibody is able to block MMP14’s activity, it has a relatively weak bond with MMP14, which is not ideal for a potential treatment. Dr Craig and his team are already working on engineering the antibody to make a new version that has a stronger bond, making it even more effective.
The team is continuing this line of research to understand whether combining this strategy with other immunotherapies, including immune checkpoint inhibitors, can be even more successful as a treatment.
It is important to know that this research is still in very early stages, and the antibody has not been tested in people yet. However, these early results are very encouraging and hold a lot of potential to improve treatments for triple-negative breast cancer.
Eileen Hoftyzer, BSc and Carolyn Goard, PhD
