Polyclonal Regulatory T cell (PolyTreg) Immunotherapy in Islet Transplantation

An Outline of This Clinical Trial

Transplant recipients require life-long dependency on immune suppression drugs to dampen the immune response to ensure the survival of the transplanted islets. The current immunosuppression regimen used in Edmonton contributes to higher success rates in islet transplantation, although the majority of patients require 2 or more islet transplants to achieve sustained insulin independence. The purpose of this trial is to infuse specialized immune-regulatory cells called polyclonal regulatory T cells (PolyTregs) into patients to determine their safety and efficacy in improving islet transplant outcomes with the hope of requiring immune suppression lower drug doses.

PolyTregs are a subtype of white blood cells that are part of one's own immune system. Studies in both humans and animal models have suggested that high numbers of PolyTregs could improve long-term organ transplantation outcomes and control Type 1 Diabetes. PolyTreg therapy is a new immunotherapy developed by our colleagues at University of California San Francisco (UCSF). PolyTregs are isolated from a participant’s whole blood. After expansion, the PolyTregs will be infused to the same participant. We believe that the infusion of PolyTregs has the potential to improve islet cell survival and function following transplant, while reducing the need for high dose immunosuppressants.

All participants will receive islet transplants following the current Edmonton islet transplant induction therapy of Alemtuzumab with Etanercept and Anakinra. Additionally, the treatment group will receive PolyTregs six weeks post-islet transplant. The Treg product will be administered via a peripheral intravenous (IV) line in approximately 20 to 30 minutes. The intravenous line will be maintained and you will be asked to remain in hospital for 24 hours. Participants will be followed for 1 year after PolyTreg infusion to assess safety and preliminary efficacy of the PolyTreg therapy. Participants from both treatment and control groups will be maintained on low dose tacrolimus and sirolimus immunosuppression.

Participants will be followed for 1 year with tests and assessments to be performed at each key study visit (30 days post-transplant, 6-, 7-, 8-, 10-, 12-, 18-, 32- and 58-weeks post-transplant). All medications and treatments used in this study are approved by Health Canada.

Patient Eligibility

Eligible participants for this study must be an adult (between the ages of 18 and 68 years old), and have been diagnosed with T1D for >5 years.