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CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice

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...

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Published in:Scientific reports 2020-02, Vol.10 (1), p.1757, Article 1757
Main Authors: Satyamitra, Merriline, Cary, Lynnette, Dunn, Dylan, Holmes-Hampton, Gregory P., Thomas, Lawrence J., Ghosh, Sanchita P.
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description 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.
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subjects 631/154
631/443
631/45
692/1807
Acute Radiation Syndrome - drug therapy
Animals
Apoptosis
Bone marrow
Bone Marrow - drug effects
CD3 antigen
CD4 antigen
Cobalt
Gamma Rays - adverse effects
Helper cells
Hematopoietic Stem Cells - drug effects
Humanities and Social Sciences
Irradiation
Lethality
Lymphocytes T
Male
Medical Countermeasures
Mice
multidisciplinary
Peripheral blood
Post-radiation
Radiation-Protective Agents - pharmacology
Science
Science (multidisciplinary)
Spleen
Splenocytes
Sternum
Whole-Body Irradiation - adverse effects
title CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice
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