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ASP2409, A Next‐Generation CTLA4‐Ig, Versus Belatacept in Renal Allograft Survival in Cynomolgus Monkeys
Author(s) -
Song L.,
Ma A.,
Dun H.,
Hu Y.,
Fujii Y.,
Kinugasa F.,
Oshima S.,
Higashi Y.,
Daloze P.,
Chen H.
Publication year - 2017
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.14039
Subject(s) - belatacept , medicine , tacrolimus , immunosuppression , calcineurin , urology , abatacept , kidney transplantation , transplantation , pharmacology , renal function , regimen , lymphoma , rituximab , kidney transplant
Belatacept is the first costimulatory blockade agent approved for maintenance immunosuppression in kidney transplant recipients. Clinical results have indicated that belatacept is associated with superior renal function and improved metabolic profile; however, higher incidence of acute rejection and posttransplant lymphoproliferative disorder are the shortcomings of this agent. In this study, ASP 2409, a new cytotoxic T‐lymphocyte associated protein 4‐immunoglobulin possessing 14‐fold higher in vitro CD 86 binding affinity than belatacept, was tested for renal allograft survival in cynomolgus monkeys. ASP 2409 monotherapy dose‐dependently prolonged renal allograft survival. Low‐dose ASP 2409 in combination with a subtherapeutic dose of tacrolimus showed much longer median survival time than monotherapy. Similar allograft survival results were observed in regimens based on high‐dose ASP 2409, belatacept, and therapeutic‐dose tacrolimus. The results of renal allograft histopathology with high‐dose ASP 2409‐based regimens were not inferior to the belatacept‐based regimen. Moreover, higher frequencies of FoxP3‐positive regulatory T cells in renal allografts were observed in ASP 2409‐ and belatacept‐based regimens compared with tacrolimus‐based regimens. No serious side effects related to ASP 2409 administration were found during the study. These data suggest that ASP 2409 is a promising candidate for calcineurin inhibitor‐sparing or ‐avoidance regimens.