Addition of IL-6 receptor blockade to Carfilzomib-based desensitization in a highly sensitized nonhuman primate model.
Academic Article
Overview
abstract
Sensitized patients, those who had prior exposure to foreign HLA antigens, are transplanted at lower rates due to challenges in finding suitable organs. Desensitization strategies have permitted highly sensitized patients to undergo kidney transplantation, albeit with higher rates of rejection. This study assesses targeting plasma cell and IL-6 receptor for desensitization in a sensitized nonhuman primate kidney transplantation model. All animals were sensitized using two sequential skin transplants from maximally MHC-mismatched donors. Carfilzomib/Tocilizumab desensitization (N=6) successfully decreased donor-specific antibody (DSA) titers and prevented expansion of B cells compared to Carfilzomib monotherapy (N=3). Dual desensitization further delayed, but did not prevent humoral rebound, as evidenced by a delayed increase in post-kidney transplant DSA titers. Accordingly, Carfilzomib/Tocilizumab desensitization conferred significant survival advantage over Carfilzomib monotherapy. A trend towards increased T follicular helper cells was also observed in the dual therapy group along the same timeline as increase in DSA and subsequent graft loss. CMV reactivation also occurred in the carfilzomib/tocilizumab group but was prevented with ganciclovir prophylaxis. In accordance with prior studies of Carfilzomib-based dual desensitization strategies, the addition of IL-6 receptor blockade resulted in desensitization with further suppression of post-transplant humoral response compared to Carfilzomib monotherapy.
