Safe use of anti-CD154 monoclonal antibody in pig islet xenotransplantation in monkeys
Safe use of anti-CD154 monoclonal antibody in pig islet xenotransplantation in monkeys
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DOI：
10.1111/xen.12283
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发表时间：
2017-01-01
影响因子：
3.9
通讯作者：
Cooper, David K. C.
中科院分区：
文献类型：
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作者：
Bottino, Rita;Knoll, Michael F.;Cooper, David K. C.
抗CD 154 mAb是一种强效共刺激阻断剂，即使在异种环境中也能有效预防排斥反应。它已被用于大多数成功的长期猪-非人灵长类动物胰岛移植模型。然而，由于在临床前和临床器官移植模型中也观察到血栓栓塞并发症，其临床使用被停止。将抗CD 154 mAb给予14只链脲佐菌素诱导的糖尿病食蟹猴猪胰岛受体，其中一些接受该试剂数月。监测猴的并发症，并经常进行血液监测。人道处死后，检查所有器官的多处活检，以确定血栓栓塞的组织学特征。抗CD 154单克隆抗体在所有猴中预防了基因工程猪胰岛的排斥反应。抗CD 154 mAb未引起明显并发症。在所有主要器官（包括大脑）的多个组织学切片中没有血栓栓塞的证据。我们的数据表明，在猪胰岛移植的糖尿病猴中，抗CD 154 mAb似乎是一种有效和安全的治疗方法，并且与血栓栓塞并发症无关。
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months. Monkeys were monitored for complications, and blood monitoring was carried out frequently. After euthanasia, multiple biopsies of all organs were examined for histological features of thromboembolism. Anti-CD154mAb prevented rejection of genetically engineered pig islets in all monkeys. No significant complications were attributable specifically to anti-CD154mAb. There was no evidence of thromboembolism in multiple histological sections from all major organs, including the brain. Our data suggest that in diabetic monkeys with pig islet grafts, anti-CD154mAb would appear to be an effective and safe therapy, and is not associated with thromboembolic complications.