Anti-CD40L

For decades, scientists have known that replacing insulin-producing islet cells could transform the lives of people living with type 1 diabetes. The challenge has not been whether transplanted islets can work — it has been how to protect them from immune rejection without exposing patients to the risks of lifelong immunosuppression.

Today, an investigational therapy known as tegoprubart is helping move that goal forward.

But this progress did not begin with a clinical trial.
It began years earlier — at the Diabetes Research Institute (DRI)— when this approach was still largely unexplored.

Modern islet transplantation became possible through pioneering advances in pancreatic islet isolation and transplantation techniques developed by leaders in the field, including Dr. Camillo Ricordi.

His development of the Ricordi Chamber made it possible to reliably isolate insulin-producing islet cells, transforming what had once been an experimental concept into a viable therapeutic approach. This work laid the technological foundation upon which today’s cell-based therapies continue to build.

But even as the field advanced, a critical challenge remained: how to protect transplanted cells from the immune system without causing harm to the patient.

At the Diabetes Research Institute, Dr. Norma Sue Kenyon focused on solving this challenge.

Her work centered on the CD40–CD40L pathway — a key regulator of immune activation — and explored a fundamentally different approach: preventing rejection through targeted immune modulation rather than broad immunosuppression.

Importantly, this work began before it had widespread external support.

“This work didn’t begin with outside funding — it began with support from the DRI Foundation. Without the foundation, it wouldn’t have been possible to move forward.”

Through extensive preclinical studies, Dr. Kenyon and her collaborators demonstrated that anti-CD40L therapies could prolong graft survival while preserving function and avoiding many of the toxicities associated with traditional immunosuppressive regimens.

These discoveries helped establish CD40L blockade as one of the most promising strategies in transplant immunology.

Today, that scientific foundation is being translated into patient care through a clinical trial underway at the University of Chicago.

In this study, tegoprubart — an investigational antiCD40L monoclonal antibody — is being evaluated as part of a calcineurin inhibitorfree immunosuppressive approach following islet transplantation.

While the trial is being conducted outside of Miami, it reflects decades of foundational work led at the Diabetes Research Institute.

Early findings from the ongoing tegoprubart islet transplantation study have shown encouraging signals:

• All participants to date have achieved insulin independence following transplantation
• Excellent glucose control has been observed, with participants maintaining HbA1c levels below 6.5%
• No severe hypoglycemia has been reported after transplantation
• No episodes of graft rejection have been observed during the current follow-up period
• No kidney or neurological toxicities typically associated with calcineurin inhibitor-based immunosuppression have been observed to date
• Sustained graft function has been maintained in the longest-treated participants for up to nearly two years

Important context:
Patients still need medication to prevent their immune system from attacking the transplanted islet cells. The difference is that researchers are testing whether tegoprubart can provide this protection while avoiding many of the side effects associated with older immunosuppressive drugs.

These findings represent early results from a limited number of patients in an ongoing study. Additional follow-up will be essential to understand long-term durability, safety, and whether immunosuppression requirements may change over time.

Dr. Norma Kenyon’s role in this research did not end with the discovery of anti-CD40L’s potential.

Today, she continues to help advance the science by studying how patients respond to tegoprubart after transplantation. Her team is focused on understanding the immune changes that occur during treatment and what those changes may reveal about long-term transplant success.

As Dr. Kenyon explains:

“We are monitoring the immunological status of the transplant patients, with a goal of understanding the changes that occur with this treatment. This may help us determine whether the graft is stable, if rejection is occurring, and whether immunosuppression could eventually be lowered.”

This deeper understanding is critical. By learning not only whether a therapy works, but why it works, researchers can continue refining approaches that may improve outcomes for people living with type 1 diabetes.

The significance of this work extends far beyond a single clinical trial.

For decades, the need for lifelong immunosuppression has been one of the greatest challenges in advancing cell-based therapies for type 1 diabetes. A more targeted approach could help make these treatments safer and more effective for more people in the future.

Advances in immune protection are becoming just as important as advances in cell replacement itself—and together, they are helping move the field closer to therapies that can restore insulin production while reducing treatment burden.

The story of tegoprubart is more than the story of a clinical trial.

It is the story of decades of scientific discovery—research that began at the Diabetes Research Institute, was supported by the Diabetes Research Institute Foundation, and continues today through ongoing innovation and collaboration.

From pioneering islet transplantation, to advancing targeted immune therapies, to studying how these treatments perform in patients, this work reflects a long-standing commitment to overcoming some of the most complex challenges in diabetes research.

Every breakthrough builds on years of dedicated research—and donor support makes that progress possible. By investing in the research of today, you help accelerate the discoveries that move us closer to a world without diabetes.