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About SickKids

October 2, 2017

SickKids scientists obtain blueprint of molecular target for blood cancer and autoimmune therapies

By Jessamine Luck, Intern, Communications & Public Affairs

Targeted therapies have represented a game-changer for many patients suffering from blood cancers and autoimmune diseases. Instead of jeopardizing the entire immune system, as many treatments currently do, targeted therapies aim to strike at the heart of these disorders and attack only the affected areas.

Researchers at The Hospital for Sick Children (SickKids) have been exploring the molecular structure of immune cell components, and how gaining an understanding of their anatomical organization can help develop future targeted therapies for blood cancers and autoimmune diseases. Dr. Jean-Philippe Julien and co-authors, Dr. June Ereño-Orbea and Taylor Sicard provide the details of their study, “Molecular basis of human CD22 function and therapeutic targeting”, published October 2 in Nature Communications.

What is CD22?

CD22 is a molecule found on the surface of B-cells that helps regulate their survival. But to understand CD22, we first have to understand how the immune system works. The immune system uses several components to protect against infections from bacteria or viruses and one of these components are B-cells. B-cells help to control the immune system and when they don’t function properly, the immune system becomes unbalanced. This can result in devastating blood cancers such as lymphoma and leukemia, and autoimmune diseases such as rheumatoid arthritis and lupus.

We’ve known for a while that CD22 is an important factor in autoimmune diseases and hyperactive B-cells. Yet, the 3D architecture of CD22 has remained elusive, preventing a molecular understanding of how it functions.

But we have a better understanding now?

That’s correct. In this study, the scientists have characterized at high magnification the properties of the human CD22 molecule. The picture of its 3D architecture provides insights into the molecule’s role in preventing autoimmunity in mammals. The scientists have also gone one step further and provided blueprints of the specific site where therapies target CD22.

What does this mean for patients?

Understanding the architecture and function of CD22 and other molecules uniquely present on the B-cell provides an opportunity to improve health outcomes. The structural blueprints now provide the basis to better understand how treatments work and offer valuable clues for the design of new treatments for B-cell dysfunction.

What are the next steps?

The authors’ results open many new lines of investigation. Now that a better understanding of the basis of B-cell regulation is available, the structural blueprints will help inform the design and fine-tuning of next-generation therapies for blood cancers and autoimmune diseases that target CD22.

Dr. Jean-Philippe Julien is a Scientist in Molecular Medicine and Assistant Professor in the Departments of Biochemistry and Immunology at the University of Toronto.

Dr. June Ereño-Orbea is a CIHR Banting and Restracomp Postdoctoral Fellow at SickKids.

Taylor Sicard is a CIHR CGS-M recipient and Restracomp Ph.D. candidate at the University of Toronto.

The work was supported by grants from the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI) John R. Evans Leaders Fund, the Ontario Research Fund and SickKids Foundation.