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  5. Anthrax Lethal Toxin Inhibits Proliferation of Human CD4+ t cells in Response to t cell Receptor Stimulation and Mitogen Stimulation
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Anthrax Lethal Toxin Inhibits Proliferation of Human CD4+ t cells in Response to t cell Receptor Stimulation and Mitogen Stimulation

 

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Technology Summary

Bacillus anthracis is a deadly disease that can be used as an efficient bioterrorism agent. Efforts are underway to develop and stockpile therapeutics for the treatment of anthrax infections. Currently, in vitro assays are available for measuring anthrax lethal toxin (LT) activity, but such assays are based on the species- and strain-specific actions of the toxin on murine macrophage cell lines. In vitro assays are needed that reflect the in vivo effects of the toxin during human infections. There is a need for bioassays based on human cell parameters.

To address this need, FDA researchers have developed a method using a human tumor CD4 T cell line to screen and determine the efficacy of anti-anthrax therapeutics. Using this method, the effects of anthrax LT were demonstrated to inhibit the proliferation of human CD4+ T cells in response to T cell receptor and mitogen stimulation. Specifically, anthrax LT was discovered to be a potent inhibitor of the MAPKK-dependent upregulation of cytokines (IL-2, IL-4 and IFN-Y) and IL-2-dependent proliferation by primary human CD4 T cells following T-cell receptor (TCR) stimulation.

Potential Commercial Applications Competitive Advantages
  • Human bioassay development for anthrax lethal toxin activity, diagnosis, and treatment
  • Determination of anthrax lethal toxin activity in human cells.

 

Development Stage: Early proof-of-concept
Inventors: David Frucht, Hui Fang
Intellectual Property:

  • United States Patent: 7,803,565 issued 9/28/2010
  • United States Patent: 8,383,359 issued 2/26/2013

Publications:

  • Fang, H. et. al. Anthrax lethal toxin has direct and potent inhibitory effects on B cell proliferation and immunoglobulin production. J Immunol. 2006 May 15;176(10):6155-61. PMID: 16670324
  • Fang, H. et al. Anthrax lethal toxin blocks MAPK kinase-dependent IL-2 production in CD4+ T cells. J Immunol. 2005 Apr 15;174(8):4966-71. PMID: 15814725
  • Cordoba-Rodriguez, R. et. al. Anthrax lethal toxin rapidly activates caspase-1/ICE and induces extracellular release of interleukin (IL)-1beta and IL-18. J Biol Xhem. 2004 May 14;279(20):20563-6. PMID: 15010463

Product Area: anthrax bioassay, diagnostic, bioterrorism
FDA Reference No: E-2004-039

Licensing Contact:
Ken Miliburne, J.D.
FDA Technology Transfer Program
Email: [email protected]
Phone: 240-402-2245

 

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