BBDC Member Profile

Elmar Jaeckel, MD

June 20, 2022
By Krista Lamb

In 2021, Dr. Elmar Jaeckel relocated to Toronto from Germany to take the role of Medical Director at the Liver Transplant Program at the University Health Network’s Transplant Centre. He also joined the faculty at the University of Toronto and became a member of the BBDC. Jaeckel’s research is focused on establishing immune tolerance in type 1 diabetes after beta cell replacement through cell and gene therapy approaches.

Trained as a gastroenterologist and hepatologist, as well as endocrinologist and diabetologist, Jaeckel brings extensive experience to the liver transplant program. However, it was Toronto’s flourishing community of researchers working on stem-cell-derived beta cells and other islet transplant programs that was of special interest to him. In particular, he is looking forward to collaborating with Dr. Trevor Reichman, who is doing islet transplantation. “The program is growing quickly, to an extent that we are now also participating in trials using stem-cell-derived beta cells by Vertex and ViaCyte and other companies,” says Jaeckel. “I hope that in the future Toronto will be a large site for biological beta cell replacement.”

Rejection and immunosuppression, which are always of concern with transplants, are major areas of interest in the Jaeckel lab, where they are aiming to create tissue-specific tolerance. “This would hopefully enable endogenous regeneration of the patient’s own islets. And because I always say the best transplantation is the one which doesn’t have to be performed, if you can rescue the patient’s own tissue, by having an immune protection shield, this would be the best,” he says. “If all the beta cells are gone, and there is no chance for regeneration, then comes the biological beta cells for replacement.”

This work to move away from systemic immunosuppression, could potentially make transplants viable for more people, as well as reducing side effects like cancer and infection. Having seen the positive results from whole pancreas transplant, which is effective for metabolic control and blood sugar regulation, but requires an organ donor and years of immunosuppression, Jaeckel hopes his research will lead to a solution that removes the need for both of these elements.

His team is using genetically-modified regulatory T cells to enable endogenous regeneration. “You have to envision this as a kind of a micro-pharmacy, because these T cells have way more than one effector function, but they will just release these effector functions locally. It’s like a Trojan horse. You bring them to the right place and then they should just locally protect with all the effector functions they have.” Jaeckel explains. “We started off taking normal regulatory T cells, which recognize beta cells as a T cell receptor. The T cell receptor is a great structure, but has the problem that it’s MHC (major histocompatibility complex) restricted, so it’s quite different, even in type 1 patients. Our strategy in the past year has been that we use a CAR, which is a chimeric antigen receptor. To make it very simple, it’s outside an antibody recognizing the beta cell. And inside, it’s the signaling domains of a T cell receptor. So basically, this brings our regulatory T cells at the site where the beta cells are, and is locally protecting them from your destruction, these cells will be made from the patient itself. It’s an autologous therapy.”

Right now, the process is being tested in liver transplant to find out if it is feasible. If successful, Jaeckel believes type 1 diabetes would be a logical next step for clinical trials. This is personally important to him, as throughout his career he has worked with people living with type 1 diabetes. While there has been much success with technology-based therapies for the condition over recent years, he knows that these options do not provide a full solution. “It’s great, but they still have to deal with their disease twenty-four hours a day, seven days a week. They have to watch this technical control of their blood sugars, and it’s still far away from a normal life. And some people, even with all this technical help, still have real problems. This is driving me to improve their lives” he says.