Controlled release formulations of IL-2, TGF-β1 and rapamycin for the induction of regulatory T cells

Siddharth Jhunjhunwala, Stephen C. Balmert, Giorgio Raimondi, Eefje Dons, Erin E. Nichols, Angus W. Thomson, Steven R. Little

Research output: Contribution to journalArticlepeer-review

Abstract

The absence of regulatory T cells (Treg) is a hallmark for a wide variety of disorders such as autoimmunity, dermatitis, periodontitis and even transplant rejection. A potential treatment option for these disorders is to increase local Treg numbers. Enhancing local numbers of Treg through in situ Treg expansion or induction could be a potential treatment option for these disorders. Current methods for in vivo Treg expansion rely on biologic therapies, which are not Treg-specific and are associated with many adverse side-effects. Synthetic formulations capable of inducing Treg could be an alternative strategy to achieve in situ increase in Treg numbers. Here we report the development and in vitro testing of a Treg-inducing synthetic formulation that consists of controlled release vehicles for IL-2, TGF-β and rapamycin (a combination of cytokines and drugs that have previously been reported to induce Treg). We demonstrate that IL-2, TGF-β and rapamycin (rapa) are released over 3-4 weeks from these formulations. Additionally, Treg induced in the presence of these formulations expressed the canonical markers for Treg (phenotype) and suppressed naïve T cell proliferation (function) at levels similar to soluble factor induced Treg as well as naturally occurring Treg. Most importantly, we show that these release formulations are capable of inducing FoxP3 + Treg in human cells in vitro. In conclusion, our data suggest that controlled release formulations of IL-2, TGF-β and rapa can induce functional Treg in vitro with the potential to be developed into an in vivo Treg induction and expansion therapy.

Original languageEnglish (US)
Pages (from-to)78-84
Number of pages7
JournalJournal of Controlled Release
Volume159
Issue number1
DOIs
StatePublished - Apr 10 2012
Externally publishedYes

Keywords

  • Controlled release PLGA
  • IL-2
  • Induced regulatory T cell
  • Rapamycin
  • TGF-beta

ASJC Scopus subject areas

  • Pharmaceutical Science

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