Ontology highlight
ABSTRACT: Background
Blocking the CD40-CD154 signal pathway has previously shown promise as a strategy to prevent allograft rejection. In this study, the efficacy of a novel fully human anti-CD40 monoclonal antibody-ASKP1240, administered as a monotherapy or combination therapy (subtherapeutic dose of tacrolimus or mycophenolate mofetil), on the prevention of renal allograft rejection was evaluated in Cynomolgus monkeys.Methods
Heterotopic kidney transplants were performed in ABO-compatible, stimulation index 2.5 or higher in the two-way mixed lymphocyte reaction monkey pairs. Animals were divided into 12 groups and observed for a maximum of 180 days. Histopathologic, hematology, and biochemistry analyses were conducted in all groups. Cytokine release (interleukin [IL]-2, IL-4, IL-5, IL-6, tumor necrosis factor, and interferon-γ) was investigated in several groups.Results
ASKP1240 prolonged renal allograft survival in a dose-dependent manner in monotherapy. Low-dose (2 mg/kg) or high-dose (5 mg/kg) ASKP1240, in combination with mycophenolate mofetil (15 mg/kg) or tacrolimus (1 mg/kg), showed a significantly longer allograft survival time compared with monotherapy groups. No obvious side effects including drug-related thromboembolic complications were found. Cytokine release was not induced by ASKP1240 administration.Conclusion
The present study indicates that ASKP1240, alone or in combination with other immunosuppressive drugs, could be a promising antirejection agent in organ transplantation.
SUBMITTER: Song L
PROVIDER: S-EPMC4175122 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
Song Lijun L Ma Anlun A Dun Hao H Hu Yanxin Y Zeng Lin L Bai Jieying J Zhang Guangzhou G Kinugasa Fumitaka F Sudo Yuji Y Miyao Yasuhiro Y Okimura Kazumichi K Miura Toru T Daloze Pierre P Chen Huifang H
Transplantation 20140801 3
<h4>Background</h4>Blocking the CD40-CD154 signal pathway has previously shown promise as a strategy to prevent allograft rejection. In this study, the efficacy of a novel fully human anti-CD40 monoclonal antibody-ASKP1240, administered as a monotherapy or combination therapy (subtherapeutic dose of tacrolimus or mycophenolate mofetil), on the prevention of renal allograft rejection was evaluated in Cynomolgus monkeys.<h4>Methods</h4>Heterotopic kidney transplants were performed in ABO-compatibl ...[more]