An NCI-designated Comprehensive Cancer Center
By Dory Benford | August 9, 2018
Last year, City of Hope introduced its groundbreaking Wanek Family Project for Type 1 Diabetes. This project, created through the generosity of the Wanek family and other like-minded visionaries, seeks to cure type 1 diabetes in a six year window.  
In the first year, we launched 16 projects cutting across multiple disciplines, including immunology, endocrinology, cellular therapeutics, nutrition and metabolism. Now, 18 months in, we are pleased with our progress and more optimistic than ever about finding a cure.

Here’s where we are so far

The Wanek team hit the ground running by redefining the disease itself. Textbooks have always described diabetes as a flaw in the immune system, but this may not be correct. Our researchers have found that diabetes is actually a disease of the beta cell. Beta cells, when stressed, send faulty signals to the immune system, and immune cells then read these signals as a threat and attack the beta cells just as they would cancer cells or infection.
This insight comes on the heels of research revealing that, even in patients with advanced disease, beta cells can be hibernating in pancreatic islets, essentially turning into stealth mode, to escape the immune system’s notice. We are already figuring out ways to jumpstart these beta cells once the immune attack has been countered.
A member of the Wanek Family Project team is working to awaken these hibernating cells with a series of proteins found in beta cells that are abnormally low in patients with diabetes. She has shown that adding these proteins to beta cells improves their function, longevity and resistance to attack.
Another team member is validating a genetic signature, or biomarker, that appears when transplanted beta cells are starting to die after a transplant. This biomarker tells us when to rush in to suppress the immune response to rescue remaining cells.
Additionally, researchers are working furiously to build beta cells from scratch so that we no longer have to rely on the short supply of islets available for transplantation. This would involve growing a limitless supply of beta cells from stem cells in our lab and infusing these into our patients.
We are also on our way to opening clinical trial with a procedure that has shown the potential in early studies to cure established type 1 diabetes. The procedure is called mixed chimerism via hematopoietic cell transplantation (HCT). Mixed chimerism is achieved when the immune systems of a patient and a donor are combined and stabilized to avoid the attack on newly introduced insulin-producing cells.
The Wanek team also saw great progress in treating diabetes complications. Many patients experience metabolic memory, the phenomenon whereby cells still act as if they are in a diabetic state, even when blood glucose is normal. This happens because persistent high blood sugar causes changes in gene expression that cells can’t seem to forget and this past year, we created and tested a drug that could have the potential to correct this affliction.
In our first year, we also succeeded in identifying immune signatures that can predict complete and sometimes long-term remission of type 1 diabetes by bone marrow transplantation, as well as immune signatures that signal the prospect of failure. This breakthrough will ultimately serve as the first evidence that the disease can be cured by precision medicine.
So, while the clock continues to tick on this important project, our exemplary Wanek team will continue to work passionately and committedly until we find a cure for type 1 diabetes patients everywhere. We don’t just want a cure soon. We want a cure now.

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