Tempering allorecognition to induce transplant tolerance with chemically modified apoptotic donor cells

D. P. McCarthy, J. Bryant, J. P. Galvin, S. D. Miller*, X. Luo

*Corresponding author for this work

Research output: Contribution to journalReview article

16 Scopus citations

Abstract

The development of organ transplantation as a therapy for end-stage organ failure is among the most significant achievements of 20th century medicine, but chronic rejection remains a barrier to achieving long-term success. Current therapeutic regimens consist of immunosuppressive drugs that are efficient at delaying rejection but are associated with significant risks such as opportunistic infections, toxicity, and malignancy. Thus, the induction of specific immune tolerance to transplant antigens is the coveted aim of researchers. The use of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (ECDI)-treated, autoantigen-coupled syngeneic leukocytes has been developed as a specific immunotherapy in preclinical models of autoimmunity and is currently in a phase II clinical trial for the treatment of multiple sclerosis. In this review, we discuss the use of allogeneic ECDI-treated apoptotic donor leukocytes (allo-ECDI-SP) as a strategy for inducing antigen-specific tolerance in allogeneic transplantation. Allo-ECDI-SP therapy induces long-term systemic immune tolerance to transplant antigens by subverting alloimmune recognition and exploiting apoptotic cell uptake pathways to recapitulate innate mechanisms of peripheral tolerance. Lastly, we discuss potential indications and challenges for transitioning allo-ECDI-SP therapy into clinical practice.

Original languageEnglish (US)
Pages (from-to)1475-1483
Number of pages9
JournalAmerican Journal of Transplantation
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1 2015

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Keywords

  • Basic (laboratory) research/science
  • T cell biology
  • cell death: apoptosis
  • dendritic cell
  • immunobiology
  • islet transplantation
  • tolerance
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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