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Pilot Study Evaluating Regulatory T Cell–Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model
Author(s) -
Lei J.,
Kim J. I.,
Shi S.,
Zhang X.,
Machaidze Z.,
Lee S.,
Schuetz C.,
Martins P. N.,
Oura T.,
Farkash E. A.,
Rosales I. A.,
Smith R. N.,
Stott R.,
Lee K. M.,
Soohoo J.,
Boskovic S.,
Cappetta K.,
Nadazdin O. M.,
Yamada Y.,
Yeh H.,
Kawai T.,
Sachs D. H.,
Benichou G.,
Markmann J. F.
Publication year - 2015
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13329
Subject(s) - allotransplantation , thymoglobulin , medicine , immunosuppression , islet , immunology , transplantation , immunotherapy , calcineurin , islet cell transplantation , regimen , immune tolerance , immune system , kidney transplantation , insulin
The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1‐ethyl‐3‐(3′‐dimethylaminopropyl)‐carbodiimide (ECDI)‐treated donor lymphoid cell infusion (ECDI‐DLI) with thymoglobulin, anti‐interleukin‐6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor‐specific T cell hyporesponsiveness and a transient absence of donor‐specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.