Some collaborations take decades. In the early 1990s, Camillo Ricordi, M.D., professor of surgery and medicine and chief of the Division of Cellular Transplantation at the Miller School’s Diabetes Research Institute (DRI), pioneered procedures to transplant insulin-producing islet cells into Type 1 diabetes (T1D) patients.

Those first islet transplants were successful, and the results were published in The Lancet in 1990. They were the first successful islet allotransplants worldwide, reversing diabetes and obtaining independence from insulin injections. But T1D is an autoimmune disorder that destroys islets, requiring a two-part procedure: transplanting the cells and modulating the immune system. In the initial islet cell transplants, Dr. Ricordi and colleagues gave patients tacrolimus, a commonly used anti-rejection drug, to control the autoimmune response. However, tacrolimus has significant side effects and ultimately failed to protect the transplanted islets. They needed a better method.

Dr. Ricordi spent the intervening decades working closely with Norma Kenyon, Ph.D., professor of surgery, vice provost for innovation and chief innovation officer for the Miller School, and others to develop an anti-rejection solution. Now, in 2024, that new approach is in clinical trials.

The drug, called tegoprubart, has the potential to revolutionize how islet and other transplants are protected. This antibody drug blocks a molecule called CD40L, which plays a major role in controlling the immune response. In addition, the drug appears to support islet survival in other ways.

“The immune system needs two signals to attack islet cells,” Dr. Ricordi said. “The first one alerts it to the potential threat; and the second one, CD40L, confirms that it’s a foreign antigen. But if we block CD40L, immune cells think the islets belong there and won’t attack them.”

The research was a slow and painstaking process and not at all linear. Tegoprubart is a modified version of an earlier drug that was abandoned because it caused blood clots. Over the years, companies have entered and exited the drug’s development process. Still, Drs. Ricordi and Kenyon stuck with it, and their perseverance has been rewarded.

“The first patient was transplanted with islets and the CD40L inhibitor in April,” Dr. Ricordi said. “It’s been a long journey, but we are finally getting close to the finish line.”

“This is just one example of the many ways we are tackling the remaining issues of preventing diabetes or replacing the missing beta cells,” added Matthias von Herrath, M.D., the DRI’s scientific director and holder of the Stacy Joy Goodman Chair. “Key areas are advancing immunotherapies — such as Dr. Ricordi’s and Dr. Kenyon’s work — and improving beta cell health, as well as developing new cutting-edge technologies, such as human organoids and living pancreatic tissue slices. The Diabetes Research Institute is a unique place where we can bridge boundaries through team science.”