Objective
This project aims to develop a therapy that delivers a natural anti-inflammatory protein, interleukin 10 (IL10), directly to transplanted islets. We will engineer a bi-functional antibody that stabilizes IL10 and directs it to the transplant site by recognizing a marker found on pancreatic beta cells.
The goal is to suppress immune activity only in the area of the graft, preserving transplant function without affecting the rest of the immune system. This work builds on our EternaBody platform, which is designed to stabilize short-lived molecules and deliver them to specific tissues. Through antibody engineering and preclinical testing, we aim to demonstrate feasibility and readiness for future clinical development.
Background Rationale
Type 1 diabetes results from the immune system destroying insulin-producing cells in the pancreas, leading to lifelong insulin dependence. While insulin therapy is lifesaving, it cannot fully replicate the body’s natural control of blood sugar, and many patients still face complications and reduced quality of life. For some, pancreatic islet transplantation offers a promising alternative by restoring natural insulin production. However, transplanted cells are at risk of being attacked by the immune system, just like any foreign tissue. To prevent this, patients are placed on lifelong immunosuppressive drugs. While these drugs protect the graft, they suppress the entire immune system and can cause serious side effects. This project addresses the need for safer, more precise ways to protect transplanted islets by focusing on tissue-targeted immune regulation, an approach that could eliminate the need for broad immunosuppression.
Description of Project
Type 1 diabetes is an autoimmune disease where the immune system mistakenly attacks the body’s own insulin-producing cells in the pancreas. For individuals with severe disease who are unable to manage their blood sugar with insulin therapy alone, a transplant of pancreatic islets offers a potential cure. However, to prevent the immune system from attacking the transplanted cells, patients must take long-term immunosuppressive drugs. These treatments often come with serious side effects, such as increased risk of infection, organ toxicity, and an overall weakened immune response. As a result, only a small number of eligible patients currently receive islet transplants, and the long-term benefits are often compromised by the toxicities of the required medications.
This project proposes a new approach to immunosuppression that is more selective and safer for patients undergoing islet transplantation. Instead of relying on general immunosuppressive drugs that affect the entire body, we aim to develop a therapeutic antibody that delivers immunosuppressive activity only to the site of the transplanted islets. This method is designed to reduce systemic toxicity while maintaining protection for the graft.
The antibody we are developing has two arms. One arm binds to a molecule that accumulates at the site of the transplanted cells. The other arm carries a naturally occurring immune-modulating protein that has the potential to calm the immune response and prevent rejection of the graft. This design allows us to direct the immunosuppressive activity precisely where it is needed, sparing the rest of the body and thereby reducing the risks associated with traditional treatment.
Our approach takes advantage of a special class of antibodies we call EternaBodies. These are conventional antibodies used in a new way to stabilize short-lived immune regulators in the body. When these immune regulators are bound to an EternaBody, their lifespan is extended and their therapeutic activity is prolonged. This allows us to maintain immune protection at the transplant site with less frequent dosing and greater control over treatment outcomes.
The research proposed in this grant will focus on developing and testing this antibody in preclinical models of type 1 diabetes and islet transplantation. We will evaluate how well the antibody binds to the transplant site, how effectively it prevents rejection, and how safe it is in terms of off-target immune suppression. Success in these studies will support further development toward human clinical trials.
If successful, this project will help solve one of the most difficult problems in the field of islet transplantation. By delivering immunosuppressive effects only where they are needed, we aim to make transplants safer and more accessible for patients with type 1 diabetes. In the long term, this strategy could also be adapted to other types of organ or cell transplants, and potentially even autoimmune diseases, offering a broad new tool for managing immune activity in a targeted way.
This work is being led by a team with deep experience in antibody development, transplant immunology, and clinical translation. Our goal is to move this innovative therapy into human studies with the aim of improving the quality of life and health outcomes for individuals living with type 1 diabetes.
Anticipated Outcome
We aim to develop a therapeutic antibody that extends the stability of IL10 and delivers it selectively to transplanted islets, reducing immune cell infiltration and promoting long-term graft survival without the need for systemic immunosuppression.
If successful, this program will not only demonstrate the feasibility of localized immune regulation but also advance a clinically relevant therapy for patients undergoing islet transplantation. It may ultimately lead to safer, more targeted treatments and establish the EternaBody platform as a foundation for additional tissue-specific immunotherapies.
Relevance to T1D
This project offers an exciting and potentially game-changing approach to one of the most persistent challenges in type 1 diabetes care — how to protect transplanted islet cells without putting the patient’s overall health at risk. By delivering immune regulation precisely where it is needed, this strategy could drastically reduce the need for toxic systemic immunosuppressive drugs, making islet transplantation a much safer and more viable option for a broader group of individuals.
For the type 1 diabetes community, the implications are profound. This therapy could shift the standard of care from managing blood sugar toward restoring natural insulin production. It brings us closer to a future where long-term insulin independence is possible without compromising the immune system or introducing serious side effects.
This work also aligns with a larger movement toward functional cures and personalized, precision medicine. It offers real hope — not just for better blood sugar control, but for renewed freedom, improved quality of life, and reduced burden of disease. With continued progress, what is now possible for a small subset of patients could soon become available to many more. For individuals and families affected by type 1 diabetes, that’s a future worth fighting for.