Major work led by Dr. André Veillette’s team at the Montreal Clinical Research Institut (IRCM), in collaboration with a group of researchers, and just published in Nature Immunology, identified a previously unknown path that prevents phagocytosis, a mechanism that promotes the immune system’s response to cancer.
The macrophages are immune system cells. One of macrophages’ roles is to engulf, or ‘eat up’ cells that are defective or dangerous, including cancer cells. This process is named phagocytosis. The macrophages can be called into action to eliminate cancer cells. However, this capacity is often defective when macrophages are forced in dormancy by the cancer cells. This is, in part, caused by an overabundance of a particular molecule called CD47 on cancer cells. CD47 prevents phagocytosis by triggering a molecule or “receptor” on macrophages named SIRPα. Agents that block the ability of CD47 to trigger SIRPα have shown promising results for treating cancer.
The research team collaborated to identify a previously unknown way by which CD47 prevents phagocytosis. They found that CD47 also blocks the molecule SLAMF7 on blood cancer cells, such as multiple myeloma and lymphoma. The researchers developed a new antibody, named Z10, that frees SLAMF7 from CD47, thereby increasing the elimination of tumour cells. When combined with other agents Z10 is highly effective against cancer cells expressing SLAMF7, at least in mice.
Why This Research Matters
Cancer remains the leading cause of death in Canada. It is estimated that two out of five Canadians will be diagnosed with cancer in their lifetime, and approximately one in four will die from the disease. The battle against cancer is thus still raging on several fronts, and the deep understanding of the immune system’s role in the growth of cancer cells is a major component of this battle.
These data suggest that Z10 could be an effective new treatment for human cancers expressing SLAMF7, including multiple myeloma and lymphoma. The Veillette team is now setting up partnerships with pharmaceutical companies to test Z10 in clinical trials.
This study was done in collaboration with the Enfu Hui’s laboratory, an expert in protein–protein interactions and immune regulation.
