A Chemogenomic Platform for Identifying Orphan Glyco-immune Checkpoints

Health Research BC is providing match funds for this research project, which is funded by GlycoNet’s Collaborative Team Grant.

This Canada-wide project is a collaboration between Prof. Landon Edgar (University of Toronto, lead PI) and Prof. Simon Wisnovsky (UBC). Both PIs research the ways in which cellular sugar molecules control the activity of immune cells. All of the cells in our body are coated with different types of sugar molecules. Cells in our immune system have ways of “tasting” these sugars. Some types of sugars taste good to our immune system, signaling that our cells are healthy and that everything is normal. Other sugars (like those attached to invading bacteria, viruses or cancer cells) taste bad to our immune cells, triggering them to activate and try to protect us from disease. Sometimes our cells can become altered in ways that lead them to produce different or abnormal types of sugar molecules on their surface. When this happens, it can lead our immune cells to either overlook unhealthy cells (in the case of cancer) or inappropriately attack healthy cells (in the case of autoimmune diseases). Understanding the details of how this happens can help us develop new drugs to treat such diseases. We face the problem, however, that these cellular sugar molecules are not like the sugar that we eat. Cellular sugars are notoriously chemically complex, making it difficult to predict exactly how specific types of sugar molecules will affect our immune system. This proposal attempts to solve this problem by using advanced genetic techniques to better understand the ways in which immune cells interact with cell-surface sugars. The goal of the project is to identify specific proteins that bind to cancer-associated sugars whose activity can then be blocked for therapeutic purposes.

End of Award Update – April 2024

Results:

With our genome-wide CRISPR screening approach, we have identified several novel immune receptors that bind tumor associated carbohydrate antigens. We are currently seeking to validate these receptors as targets in immune oncology assays.

Impact & Potential Influence:

There is an urgent need to uncover novel targets for cancer immunotherapy. Our work has uncovered several tractable immune receptors that may be excellent targets for the development of novel immune checkpoint inhibitor therapeutics. In the long-run, our work lays the foundation for the development of broad-spectrum immunotherapies for a range of different cancer subtypes.

Next steps:

We are currently putting a grant application together to get this project funded in the longer term by the Cancer Research Society. We hope to publish a small methods-focused paper on this research in the coming year.