Background & Purpose

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BACKGROUND AND PURPOSE

JDRF is committed to advancing the development of beta cell replacement therapies that are able to restore glycemic control and eliminate the need for exogenous insulin administration in people with T1D. It has been shown that pancreatic islet transplantation is efficacious in improving metabolic control, preventing severe hypoglycemia, reducing exogenous insulin requirements, and improving quality of life in patients with medically unstable T1D. Despite significant progress in the development of alternative renewable sources of insulin producing cells to overcome the shortage of donor tissue, major scientific and technical challenges in overcoming recurring autoimmunity and allogeneic immune rejection remain which must be addressed before beta cell replacement can be widely implemented as a cure for established T1D. The reliance on systemic administration of immunosuppressive drugs to protect the cell graft from the recipient’s immune response is one key limitation which calls for the development of safer and better alternatives capable of ensuring long-term graft survival and function.

The field of immunology has made significant advances thanks to efforts in the fight against cancer and other autoimmune diseases as well as organ transplantation. These include a better understanding of mechanisms of activation and regulation of the immune system and the development of novel biologics and immunotherapies targeting immune checkpoint, co-stimulation, and immunometabolic pathways. Similarly, the field of biomedical engineering has made significant progress in the development of novel materials and systems for targeted and controlled drug delivery. These systems enable delivery of signals or drugs to specific tissues, cells, or cell compartments in a manner that results in therapeutic efficacy while evading the unwanted side effects encountered when delivering drugs systemically. At the intersection of these two fields lies the more recently established discipline of immunoengineering which seeks to integrate engineering tools and principles with those from immunology to develop novel therapeutic strategies to modulate the immune system in a highly specific, targeted, and controlled manner. In the context of beta cell replacement therapy and T1D, these approaches could be employed to target and exploit mechanisms of immune cell recruitment or homing, antigen presentation and recognition, and immune cell activation and regulation to effectively subvert and/or modulate undesired immune reactivity against implanted cell products towards more tolerogenic responses in vivo.