Localized Immune Tolerance for Safer and Effective Type 1 Diabetes Therapy
This engineered cell therapy combination was developed to treat Type 1 diabetes. Type 1 diabetes (T1D) is a chronic autoimmune disease caused by an autoimmune attack on the insulin-producing pancreatic beta cells. It affects approximately 8.4 million people worldwide, with prevalence expected to rise to 13.5 million by 2040. In the United States alone, T1D carries a substantial clinical and economic burden exceeding $16 billion, driven by lifelong insulin dependence and serious complications such as cardiovascular disease and kidney failure. Available curative approaches, such as pancreas or islet transplantation, are limited by donor shortages and require lifelong immunosuppression, increasing the risks of infection and cancer. Therefore, there is a critical need for strategies for providing localized immune protection without compromising overall immune function.
Human pluripotent stem cells (hPSCs) offer an inexhaustible source of insulin-producing beta cells for transplantation. However, transplanted hPSC-derived beta cells remain vulnerable to both alloimmune and autoimmune rejection. Existing immune evasion strategies to reduce rejection, such as deleting major histocompatibility complex (MHC) molecules or overexpressing immune checkpoint proteins, can reduce rejection but may also compromise immune surveillance, creating safety concerns. The global cell therapy market, valued at $11.2 billion in 2024, is projected to reach $28.7 billion by 2034, with a 10.1% CAGR, positioning this therapy as a transformative solution for T1D treatment.
Researchers at the University of Florida have developed a combination engineered cell therapy that co-engineers hPSC-derived beta cells and regulatory T cells (Tregs) to provide localized immune protection. This approach introduces a biologically inert surface marker on hPSCs and equips Tregs with a chimeric antigen receptor (CAR) targeting that marker, enabling precise immune tolerance at the graft site without systemic immunosuppression, offering a safer and more effective solution for beta cell replacement therapy.
Application
Combination engineered cell therapy for protecting transplanted insulin-producing cells from immune attack, reducing rejection risk, and improving long-term insulin independence in Type 1 diabetes patients
Advantages
- Localized immune protection at the graft site, reducing reliance on chronic systemic immunosuppression and its associated health risks
- Maintains immune surveillance, allowing the immune system to continue responding to infections and malignancies
- Offers a scalable and renewable source of insulin-producing beta cells from pluripotent stem cells, overcoming donor shortages
- Adaptable for other autoimmune diseases and organ transplantation, expanding its clinical and commercial potential
- Combines stem cell engineering with CAR-Treg immunotherapy, ensuring long-term graft survival and functional insulin production
Technology
This cell therapy integrates stem cell engineering and CAR-Treg immunotherapy to create a targeted immune-protective niche around transplanted beta cells. Human pluripotent stem cells are first engineered to express an inert surface protein, the truncated epidermal growth factor receptor (EGFRt). These modified stem cells are then developed into insulin-producing beta cells. Next, regulatory T cells (Tregs) are engineered with a special receptor, a chimeric antigen receptor (CAR), that recognizes the EGFRt marker on the beta cells. When both cell types are transplanted together, the CAR-Tregs detect the marker and activate, creating a protective immune shield around the beta cells. This prevents the body’s immune system from attacking the graft while still allowing normal immune function elsewhere. The process has demonstrated proof of concept both in vitro and in vivo, showing sustained graft survival and effective functional insulin secretion in preclinical models. By decoupling localized tolerance from global immunosuppression, this platform offers a conceptually new route to durable beta cell replacement in T1D and provides a generalizable framework for protecting other stem cell–derived tissues from immune rejection. It is a targeted, safe, and scalable solution for restoring insulin independence in patients with Type 1 diabetes.
Brochure
