Challenge: Because of their immunosuppressive properties, galectins play a critical role in many diseases, most notably in cancer. Some galectins can suppress the immune response by inducing the death of cells that are protecting against cancer cells development. Galectins can also promote tumor cell growth by preventing tumor infiltration by immune cells. For these reasons, there was an increased interest in recent years to use galectins as therapeutic targets, especially for cancer with limited treatment options like triple negative breast cancers (TNBC). However, development of highly selective galectin inhibitors that minimize off-target effects has been virtually impossible to achieve given the striking structural similarity between the different members of this family of proteins. High selectivity is a critical issue because tumor cells express a relatively large repertoire of galectins.

Solution: Since dimerization is essential for galectins immunosuppressive functions, interfering with the formation of homodimers provides a unique opportunity to develop highly specific galectin inhibitors. In this project, the research team combines the unique properties of camelid antibodies (nanobodies) and a new mechanism of action (“dimer interference”) to generate highly specific galectin targeting inhibitors. More specifically, these inhibitors will enable fundamental research on the role of galectins in cancer and the testing of anti-galectin therapeutics as a next wave of cancer immunotherapies. Pre-clinical studies will be performed with relevant lead nanobodies. They will be tested for their therapeutic efficacy in vivo in a mouse model of TNBC.

Expected achievements/Impact: This project will generate a set of tools that will enable pharmaceutical companies to interrogate the role of galectins in their drug discovery programs. This technology platform will lead to the development of a large and diverse panels of functional nanobodies that are antagonists against galectins, including less well-known galectins. Anti-galectin therapeutics could represent an effective tool to fight against adverse effects of galectins, especially for hard to treat cancers like TNBC where some galectins have been shown to play an important role in tumor progression.