文章基本信息

标题：CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice
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作者：Merriline Satyamitra ; Lynnette Cary ; Dylan Dunn 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-15
DOI：10.1038/s41598-020-58186-1
出版社：Springer Nature
摘要：Bone marrow failure and hematopoietic damage is one of the major consequences of irradiation-induced lethality. There is an immediate need to develop medical countermeasures (MCMs) to combat irradiation-induced lethality. We tested the efficacy of CDX-301, developed by Celldex Therapeutics Inc., in mice exposed to Co-60 gamma total body irradiation (TBI). The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to TBI. A single dose of CDX-301 administered 24 h prior to 24 h post-exposure conferred significant survival. Accelerated recovery from irradiation-induced peripheral blood cytopenia, bone marrow damage as well as apoptosis in sternum was observed in mice pre-treated with CDX-301. Analysis of splenocytes revealed alterations in T cell profiles that were dependent on the time of drug administration. Prophylactic treatment of CDX-301 resulted in increased splenic CD3+ T cells, specifically CD4+T helper cells, compared to splenocytes from non-irradiated mice. These results indicate that CDX-301 is a promising radiation countermeasure and demonstrate its capability to protect cells within hematopoietic organs. These data support potential use of CDX-301, both pre- and post-radiation, against hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.