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Tempering Allorecognition to Induce Transplant Tolerance With Chemically Modified Apoptotic Donor Cells Open Access (recommended)

Descriptions

Resource type(s)
Review
Keyword
Tolerance
Transplant
Apoptotic cells
Rights
Attribution 3.0 United States

Creator
Galvin, John P
Miller, Stephen D
Luo, Xunrong
McCarthy, D. P.
Bryant, J.
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 Bibliographic Citation
McCarthy DP, Bryant J, Galvin JP, Miller SD, Luo, X (2015) Tempering Allorecognition to Induce Transplant Tolerance With Chemically Modified Apoptotic Donor Cells. Am J Transplant 15(6):1475-1483.
Publisher
DigitalHub. Galter Health Sciences Library
Date Created
2015
Language
English
Subject: MESH
Transplantation Tolerance
Transplantation Immunology
Transplantation, Homologous
Histocompatibility Antigens
DOI
10.18131/G37G63
ARK
ark:/c8131/g37g63

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