Transplantation Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Transplantation Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pathology, University of Washington School of Medicine, Seattle, Washington.
Biol Blood Marrow Transplant. 2018 Jan;24(1):50-54. doi: 10.1016/j.bbmt.2017.09.010. Epub 2017 Sep 25.
In murine model systems inducible costimulator (ICOS) signaling has been implicated in the formation of chronic graft-versus-host disease (GVHD). Previously, we showed that chronic GVHD can be reproducibly produced in the dog hematopoietic cell transplantation (HCT) model and that ICOS expression is upregulated on T cells in dogs with chronic GVHD. The goal of the present study was to determine whether administration of a short course of anti-canine ICOS mAb could alter the rapid and progressive course of chronic GVHD. Five dogs underwent HCT from dog leukocyte antigen mismatched unrelated donors after total body irradiation. Postgrafting immunosuppression consisted of methotrexate (days 1, 3, 6, and 11) and cyclosporine (days -1 through 78). Anti-ICOS mAb (3 injections, 72 hours apart) was administered upon diagnosis of GVHD. One dog failed to respond to anti-ICOS mAb therapy and succumbed to chronic GVHD in a time course similar to control untreated dogs. Overall, anti-ICOS-treated dogs experienced a significant prolongation in survival from the time of diagnosis of chronic GVHD compared with control dogs. Within the limitations of the number of study dogs we suggest that a short course of anti-ICOS mAb may be useful in the treatment of chronic canine GVHD.
在诱导共刺激因子（ICOS）信号的鼠模型系统中，已涉及慢性移植物抗宿主病（GVHD）的形成。此前，我们表明，慢性 GVHD 可在犬造血细胞移植（HCT）模型中可重复产生，并且在患有慢性 GVHD 的犬中，ICOS 表达在 T 细胞上上调。本研究的目的是确定短期给予抗犬 ICOS mAb 是否可以改变慢性 GVHD 的快速和进行性病程。5 只犬在全身照射后接受来自犬白细胞抗原不合的无关供体的 HCT。移植后免疫抑制包括甲氨蝶呤（第 1、3、6 和 11 天）和环孢素（第-1 天至第 78 天）。在诊断 GVHD 时给予抗 ICOS mAb（3 次注射，间隔 72 小时）。一只犬对抗 ICOS mAb 治疗无反应，并以类似于对照未治疗犬的时间进程死于慢性 GVHD。总体而言，与对照犬相比，接受抗 ICOS 治疗的犬从慢性 GVHD 诊断开始的生存时间显著延长。在研究犬数量的限制内，我们建议短期给予抗 ICOS mAb 可能对治疗慢性犬 GVHD 有用。
