To date, there are no safe and effective drugs available for protection against ionizing radiation damage. Therefore, a great need exists to identify and develop non-toxic agents that will be useful as radioprotectors or postirradiation therapies under a variety of operational scenarios. We have developed a new pharmacological agent, CBLB613 (a naturally occurring Mycoplasma-derived lipopeptide ligand for Toll-like receptor 2/6), as a novel radiation countermeasure. Using CD2F1 mice, we investigated CBLB613 for toxicity, immunogenicity, radioprotection, radiomitigation and pharmacokinetics. We also evaluated CBLB613 for its effects on cytokine induction and radiation-induced cytopenia in unirradiated and irradiated mice. The no-observable-adverse-effect level of CBLB613 was 1.79 mg/kg and 1 mg/kg for single and repeated doses, respectively. CBLB613 significantly protected mice against a lethal dose of 60Co γ radiation. The dose reduction factor of CBLB613 as a radioprotector was 1.25. CBLB613 also mitigated the effects of 60Co γ radiation on survival in mice. In both irradiated and unirradiated mice, the drug stimulated induction of interleukin-1β (IL-1β), IL-6, IL-10, IL-12, keratinocyte-derived chemokine, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-1α. CBLB613 also reduced radiation-induced cytopenia and increased bone marrow cellularity in irradiated mice. Our immunogenicity study demonstrated that CBLB613 is not immunogenic in mice, indicating that it could be developed as a radioprotector and radiomitigator for humans against the potentially lethal effects of radiation exposure.
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1 May 2012
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December 16 2011
CBLB613: A TLR 2/6 Agonist, Natural Lipopeptide of Mycoplasma arginini, as a Novel Radiation Countermeasure
Vijay K. Singh;
Vijay K. Singh
1
a Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland
b Department of Radiation Biology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland
1 Address for correspondence: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Ave., Bethesda, MD 20889-5603; e-mail singh@afrri.usuhs.mil.
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Elizabeth J. Ducey;
Elizabeth J. Ducey
a Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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Oluseyi O. Fatanmi;
Oluseyi O. Fatanmi
a Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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Pankaj K. Singh;
Pankaj K. Singh
a Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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Darren S. Brown;
Darren S. Brown
a Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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Andrei Purmal;
Andrei Purmal
c Cleveland BioLabs, Inc., Buffalo, New York
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Vera V. Shakhova;
Vera V. Shakhova
c Cleveland BioLabs, Inc., Buffalo, New York
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Andrei V. Gudkov;
Andrei V. Gudkov
c Cleveland BioLabs, Inc., Buffalo, New York
d Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York
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Elena Feinstein;
Elena Feinstein
c Cleveland BioLabs, Inc., Buffalo, New York
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Alexander Shakhov
Alexander Shakhov
2
c Cleveland BioLabs, Inc., Buffalo, New York
2 Co-corresponding author: Cleveland BioLabs, Inc., 73 High St. Buffalo, NY 14203; e-mail ashakhov@cbiolabs.com.
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Radiat Res (2012) 177 (5): 628–642.
Article history
Received:
April 19 2011
Accepted:
November 09 2011
Citation
Vijay K. Singh, Elizabeth J. Ducey, Oluseyi O. Fatanmi, Pankaj K. Singh, Darren S. Brown, Andrei Purmal, Vera V. Shakhova, Andrei V. Gudkov, Elena Feinstein, Alexander Shakhov; CBLB613: A TLR 2/6 Agonist, Natural Lipopeptide of Mycoplasma arginini, as a Novel Radiation Countermeasure. Radiat Res 1 May 2012; 177 (5): 628–642. doi: https://doi.org/10.1667/RR2657.1
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