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 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:

As a means of treating endotoxemia and septic peritonitis

Competitive Advantages:

No current therapeutics are available to treat septic shock

Development Stage:

Pre-clinical

Inventors:

John E. Coligan, NIAID, NIH

Oliver H. Voss, NIAID, NIH

Konrad Krzewski, NIAID, NIH

Publications: Voss, Oliver H., et al. "Lipopolysaccharide-induced CD300b receptor binding to toll-like receptor 4 alters signaling to drive cytokine responses that enhance septic shock." Immunity 44.6 (2016): 1365-1378.

Intellectual Property: HHS Reference No. E-112-2016/0 - US Patent Application No. 62/308,144 filed 03/14/2016

Licensing and Collaborative Research Opportunity: