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Updated: May 24, 2026
Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres
Published on: November 5, 2016
Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term triple therapy
1Harvard Medical School, Department of Surgery, Transplant Institute at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Boston, MA, USA. mkoulman@bidmc.harvard.edu
Abstract:
Preclinical studies in nonhuman primates (NHP) are particularly useful to evaluate the safety and efficacy of new therapeutic proteins developed for use in clinical transplantation. We hypothesized that a treatment that selectively destroys activated cytopathic donor reactive T cells while sparing resting and immunoregulatory T cells in a mouse model might also produce long-term drug-free engraftment and tolerance without the hazards of lymphopenia in the challenging nonhuman primate islet allograft model. Short-term treatment with a regimen consisting of rapamycin, and IL-2.Ig plus mutant antagonist-type IL-15.Ig cytolytic fusion proteins (triple therapy) posttransplantation results in prolonged, drug-free engraftment of cynomolgus islet allografts. Moreover slow progressive loss of islet function in some recipients was not associated with obvious pathologic evidence of rejection.
Insights
This study shows that a short-term triple therapy can lead to long-term, drug-free islet allograft engraftment in nonhuman primates. This approach avoids lymphopenia and offers a promising strategy for transplantation tolerance.
Area of Science:
- Immunology
- Transplantation Biology
- Preclinical Research
Background:
- Preclinical studies in nonhuman primates (NHP) are crucial for assessing new therapeutic proteins for clinical transplantation.
- Developing strategies for long-term, drug-free engraftment and tolerance in transplantation is a significant challenge.
Purpose of the Study:
- To evaluate a novel therapeutic approach for achieving long-term, drug-free islet allograft engraftment and tolerance in nonhuman primates.
- To test if selective destruction of activated T cells can prevent rejection without causing lymphopenia.
Main Methods:
- Utilized a nonhuman primate islet allograft model (cynomolgus macaques).
- Administered a short-term triple therapy post-transplantation, including rapamycin, IL-2.Ig, and mutant antagonist-type IL-15.Ig cytolytic fusion proteins.
- Monitored islet allograft engraftment, function, and signs of rejection.
Main Results:
- Short-term triple therapy resulted in prolonged, drug-free engraftment of cynomolgus islet allografts.
- Some recipients experienced slow, progressive loss of islet function without clear pathologic evidence of rejection.
- The treatment strategy aimed to spare resting and immunoregulatory T cells.
Conclusions:
- This triple therapy regimen shows potential for achieving long-term, drug-free islet allograft acceptance in a nonhuman primate model.
- The approach may offer a safer alternative to traditional immunosuppression by avoiding generalized lymphopenia.
- Further investigation is warranted to understand the mechanisms of slow graft function loss.
