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

• 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.
• Format: Article
• Language: English
• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58186-1

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.