Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model

Authors
TURAN KANMAZJOHN H. FECHNER JR.JOSE TORREALBAHYOUNG TAE KIMYINCHEN DONGTERRY D. OBERLEYJACQUELINE M. SCHULTZDEBRA D. BLOOMMASAAKI KATAYAMAWASIM DARJUDIT MARKOVITSWALTER SCHULERHUAIZHONG HUMAJED M. HAMAWYSTUART J. KNECHTLE
Department
Dept. of Surgery (외과학)
Issue Date
2004
Citation
Transplantation, Vol.77(6) : 914-920, 2004
ISSN
0041-1337
Abstract
Background. This study assesses the safety and efficacy of the novel human anti-human CD154 monoclonal antibody ABI793 in rhesus monkeys. Methods. Outbred rhesus monkeys were used for renal transplantation from major histocompatibility complex-mismatched donors. Seven recipients were treated with ABI793, and six untreated recipients were used as controls. Graft function was monitored by urine output, serum creatinine, and renal biopsy. Phenotypic analysis of peripheral blood lymphocytes and mixed lymphocyte reaction were performed before transplantation and periodically after transplantation. Anti-donor major histocompatibility complex class I antibody levels were measured at the time of sacrifice. Results. Monkeys in the treated group demonstrated prolonged graft survival compared with controls. One monkey was sacrificed because of a urine leak on postoperative day 13. Three monkeys were sacrificed because of acute rejection (days 44, 149, and 158). Two monkeys were sacrificed because of chronic active rejection (days 154 and 221). One monkey was sacrificed on day 139 without rejection to observe the effects of ABI793 in the absence of rejection. There were no obvious clinical side effects of ABI793, but microscopic thromboembolic changes were observed in two monkeys. Lymphocyte subsets remained unaltered in all monkeys. Mixed lymphocyte reaction showed nonspecific suppression 6 weeks after transplantation. The monkeys with chronic active rejection showed relatively strong alloantibody responses. Conclusions. ABI793 induces prolonged renal allograft survival in rhesus monkeys. Nevertheless, thromboembolic complications may occur and chronic allograft nephropathy may develop after anti-CD154 treatment is discontinued.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34708
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
Keimyung Author(s)
김형태
Full Text
https://insights.ovid.com/pubmed?pmid=15077037
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