Breakthrough T1D Request for Applications: Mechanisms of Graft Acceptance in Clinical Islet Transplantation

Funding over a maximum of two years to support research using existing clinical datasets that will expand understanding of mechanisms contributing to long term survival/function and immune tolerance toward transplanted islet grafts to treat type 1 diabetes.

Breakthrough T1D, based in the United States, is an international organisation that funds innovative research in pursuit of its mission to advance the treatment, prevention and cure of type-1 diabetes (T1D).

Breakthrough T1D has issued a Request for Applications – Mechanisms of Graft Acceptance in Clinical Islet Transplantation – to solicit proposals for research, using exising clinical datasets, to expand understanding of mechanisms contributing to long term survival/function and immune tolerance toward transplanted islet grafts to treat type 1 diabetes (T1D).

One of Breakthrough T1D’s goals (as per its research strategy) is to accelerate the development of therapies capable of restoring metabolic control and insulin independence in T1D through the transplantation of insulin-producing cells.

While pancreatic islet transplantation has been efficacious in improving metabolic control and preventing severe hypoglycemia in a select group of patients with medically unstable T1D, significant further advancements are required in order to recommend islet transplantation for broader patient populations. The reliance on chronic systemic immunosuppression to limit immune rejection of the cell graft stands as one of the major barriers to the adoption of islet transplantation for the broader patient population.

Breakthrough T1D aims to enable the scientific community to address the challenges of pancreatic islet transplantation with the ultimate goal of accelerating the development of safe and effective beta cell replacement therapies that are available to all individuals living with T1D. There is a lack of a clear mechanistic understanding of what contributes to one patient’s transplant success or another patient’s transplant failure. Developing a deeper understanding of the factors contributing to differential survival and function across the spectrum of transplant outcomes will help inform the design of next generation islet replacement that are suitable for a broader patient population.

Accordingly, this funding  opportunity aims to advance understanding of graft acceptance and immune tolerance in islet transplantation using existing clinical data. Breakthrough T1D is soliciting Letters of Intent from investigators who have access to such datasets with the aim to ultimately support long-term islet survival and improve therapeutic outcomes of current and future islet transplantation approaches for T1D.

Relevant datasets may include National Institutes of Health NIDDK Central Repository studies, CIT02 through CIT08, pan-CIT, and Collaborative Islet Transplant Registry samples/data, or center specific datasets from national islet transplant programmes and registries, and clinical trials. Industry sponsored trials and/or trials using alternative sources of insulin producing cells (eg human stem cell-derived islets or porcine sources) are also of interest.

Examples of topics pertinent to this call include but are not limited to:

• Using clinical datasets to identify biomarkers/signatures of beta cell stress or immune rejection to better measure and predict graft failure prior to decline in c-peptide and/or glycemic control.
• Single cell profiling of immune cells from patients undergoing islet transplantation as correlates of therapeutic outcomes, ideally with longitudinal sampling.
• Analysis of immune populations in clinical datasets testing alternative immune protection strategies such as immunomodulatory therapy.
• High dimensional -omic profiling of banked serum or blood samples from islet transplant recipients as correlates of therapeutic outcomes.
• Investigating common signals within other transplant types, such as liver or kidney, which exhibit immune tolerance that may apply to islet transplant.