title: Tempering allorecognition to induce transplant tolerance with chemically modified apoptotic donor cells.
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.
authors: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors: D P
authors: DP
authors: McCarthy
authors: Department of Medicine, Feinberg School of Medicine, Northwestern University, Evanston, IL.
authors: J
authors: J
authors: Bryant
authors: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.|Department of Medicine, Feinberg School of Medicine, Northwestern University, Evanston, IL.
authors: J P
authors: JP
authors: Galvin
authors: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors: S D
authors: SD
authors: Miller
authors: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.|Department of Medicine, Feinberg School of Medicine, Northwestern University, Evanston, IL.|Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Evanston, IL.
authors: X
authors: X
authors: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005022:Ethyldimethylaminopropyl Carbodiimide / Q000494:pharmacology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology* / Q000502:physiology; D007111:Immunity, Cellular / Q000276:immunology / Q000502:physiology; D007113:Immunity, Innate / Q000276:immunology* / Q000502:physiology; D007167:Immunotherapy / Q000379:methods; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D023421:Models, Animal; D014019:Tissue Donors; D014184:Transplantation, Homologous; D019737:Transplants / Q000166:cytology / Q000276:immunology* / Q000502:physiology
chemical_list: D016207:Cytokines; D005022:Ethyldimethylaminopropyl Carbodiimide
keywords: Basic (laboratory) research/science; T cell biology; cell death: apoptosis; dendritic cell; immunobiology; islet transplantation; tolerance; translational research/science