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Localized Immunomodulation in Beta Cell Replacement

Deadlines are 5:00 PM (Eastern). No extensions will be granted.

Milestone Date Status
Letter of Intent Required Sep 27, 2018 Passed
Application Nov 15, 2018 Passed
Award Notification May 01, 2019 Passed
Earliest Start Jun 01, 2019 Passed

Background & Purpose

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JDRF is committed to the development of beta cell replacement therapies to restore glycemic control and eliminate the need for exogenous insulin administration in people with T1D. Pancreatic islet transplantation has been efficacious in improving metabolic control, preventing severe hypoglycemia, 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 remain that must be addressed before beta cell replacement is widely incorporated into the clinical management of established T1D. One key limitation is the need for systemic administration of immunosuppressive drugs to protect the cell graft from the recipient’s immune response.


The advent of the Edmonton protocol signified a major breakthrough in clinical islet transplantation by significantly improving outcomes in patients that underwent the procedure as reflected by stable glycemia, reduction in hemoglobin A1c (HbA1c), and elimination of hypoglycemia for several years.1,2 However, most of these patients still failed to maintain insulin independence for more than 5 years due to graft failure. Moreover, the use of immunosuppressive drugs is associated with serious adverse side effects and can impair beta cell function.3-5 Alternative approaches being explored for providing immune protection include encapsulation of cells in permselective membranes that allow exchange of nutrients, glucose, and insulin but block immune cells and other immune effectors from recognizing the graft.6-13 Although progress has been promising, the foreign body reaction and ensuing fibrotic encapsulation of implanted materials paired with limitations on mass transfer and nutrient delivery remain a challenge.

More recently, the emerging field of immuno-engineering has come to the forefront of efforts to develop technologies to control the patient’s innate and adaptive immune responses.14-24 These approaches employ various strategies targeting mechanisms of immune cell recognition and activation which could be exploited to direct the host response to implanted materials and/or cells towards a wound healing and/or tolerogenic response, as opposed to an inflammatory and/or effector response. Local immunomodulation at the graft site is highly desirable, as it could obviate the need for harsh and burdensome systemic immunosuppression regimens and perhaps even encapsulation barriers. Therefore, JDRF wishes to support research into novel strategies for localized modulation of the host response to implanted materials and development of immunomodulatory therapeutics to provide graft protection at the transplant site leading to long-term graft function.