Another significant step is being achieved by researchers at the DRI on the lengthy journey to bring islet cell transplantation closer to reality for individuals with type 1 diabetes.
The monoclonal antibody AT-1501 is an immunosuppressive drug that addresses a key challenge in the islet transplant field: immune rejection. Patients who receive islet cells from donors often experience their immune system attacking these new islets, resulting in rejection. A recent study demonstrates that the antibody can effectively tackle this issue and, notably, overcome a significant obstacle that the previous monoclonal antibody with such potential faced: blood clotting.
“It’s really very exciting,” said Norma Sue Kenyon, Ph.D., professor of surgery at the Diabetes Research Institute (DRI), chief innovation officer of the Miller School of Medicine and vice provost for innovation at the University of Miami. “AT-1501, which targets one important molecule from the immune system, is also anti-inflammatory and prevents the ultimate development of antibodies against the donated cells. So, it’s just really proven to be very impactful.”
Dr. Kenyon and her team at the DRI, in collaboration with researchers from Duke University, examined the antibody using a kidney transplant model, and conducted trials on AT-1501. This investigation has yielded encouraging outcomes, revealing that the antibody supported the survival of both islet cells and kidney transplants, minimized inflammation, and avoided inducing blood clotting. These findings were published online on August 30th in the journal Science Translational Medicine.
The AT-1501 predecessor, another antibody known as Hu5c8, was being assessed in other conditions and transplant settings. “Some patients experienced blood clots, and a couple actually died,” Dr. Kenyon said. “So, despite the tremendous promise of intervening in this costimulatory pathway, that really just ― boom ― brought things to a halt.”
Delving deeper into the research
The team, consisting of the DRI and Duke University, each conducted experiments with islet transplantation or kidneys. AT-1501 either as a standalone treatment or in combination with other commonly used immunosuppressive agents.
“The results were great,” Dr. Kenyon said.
When combined with other drugs, the antibody showcased even more impressive results – a significant achievement in insulin independence, leading to improved weight gain and fewer side effects compared to conventional anti-rejection strategies. Additionally, it seems to provide a more lasting effect. This suggests that if the studies continue to succeed, individuals with type 1 diabetes who undergo islet cell transplantation might not be required to take lifelong immunosuppression.
Insulin-positive pancreatic islet with intact insulin-producing cells (red cells) at one year after transplant.
Resources:
Science Translational Medicine: https://www.science.org/doi/10.1126/scitranslmed.adf6376