CD300b Expression Exacerbates Endotoxemia and Septic Peritonitis


The innate immune system is the first line of host defense against invading pathogens. Lipopolysaccharides (LPS), present in gram-negative bacteria membranes, cause strong immune responses following detection by the Toll-like receptor 4 (TLR4) on immune cells. This detection results in the release of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, and interferon gamma, to assist with clearance of the infectious insult. In parallel, interleukin-10 (IL-10), an anti-inflammatory cytokine, is induced to limit the immune response. This is because unchecked immune activation leads to a more severe immunopathology, such as septic shock and subsequently death. Current therapies to treat sepsis are ineffective, and clinical trials based on neutralization of specific inflammatory cytokines have failed.

The inventors, listed below, have discovered that CD300b is a LPS binding receptor. This interaction results in a reduced IL-10 production, leading to an amplification of lethal inflammation. In vitro, anti-CD300b antibodies block LPS binding to CD300b, stopping association with TLR4 and CD14 and increases IL-10 levels. In vivo, administration of anti-CD300b antibodies protects animals from septic shock, due to a reduce level of pro-inflammatory cytokines but subsequent increase in the anti-inflammatory cytokine, IL-10.

Potential Commercial Applications: Competitive Advantages:
  • As a means of treating endotoxemia and septic peritonitis.
 
  • No current therapeutics are available to treat septic shock.


Inventors:

John Coligan (NIAID)  ➽ more inventions...

Oliver Voss (NIAID)  ➽ more inventions...

Konrad Krzewski (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 62/308,144
PCT Application No. PCT/US2017/021654

Publications:
Voss OH, et al. PMID 27261276

Collaboration Opportunity:

The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further co-develop CD300b antagonists. For collaboration opportunities, please contact Chris Kornak at chris.kornak@nih.gov or 240-627-3705.


Licensing Contact:
Christopher Kornak, J.D.
Email: chris.kornak@nih.gov
Phone: 240-627-3705

OTT Reference No: E-112-2016-0
Updated: Jun 11, 2018