CBLB502: a promising radiation counter measure

The research program aims to identify and develop pharmacological radiation countermeasures to prevent, mitigate, and treat the acute radiation syndrome. Several promising radiation countermeasures are currently in various stages of development. CBLB502 (truncated flagellin, a toll-like receptor-5 agonist and NF-kappaB activator) is one of the most promising radiation countermeasures. The ability of CBLB502 to modulate blood cytokine levels in mice and nonhuman primates (NHP) has been tested with the objective of identifying cytokines as biomarkers of drug efficacy against radiation damage. CBLB502 was evaluated for immunogenicity and also tested in NHP for efficacy against the LD20/40 dose of Cobalt-60 gamma-radiation. CBLB502 induced maximum levels of G-CSF within 2-8 h. In addition to G-CSF, CBLB502 also stimulated production of both IL-6 and keratinocyte derived chemokine (IKC) in mice. The induced cytokine spectrum of CBLB502 in NHP was found to be very similar to that in mice. In both species, G-CSF, IL-6 and KC (or IL-8 in NHP) levels were correlated with drug dose. The CBLB502 dose dependence of cytokine levels coincided with CBLB502 dose-dependent radioprotection in mice and NHP. CBLB502 was not immunogenic. The results suggest that CBLB502 is a promising radiation countermeasure and specific cytokines may serve as biomarkers for efficacy, and may prove to be useful as a predictor of outcome. Potential impact to mission/war fighter: CBLB502 can be used after exposure to radiation in the field in the future. Cytokine levels may be useful as a surrogate marker for radiation countermeasure efficacy