The identification of the coinhibitory receptor 2B4 and its ligand CD48 as targets for the treatment of sepsis.
- A target for the prevention of mortality during sepsis.
- Blocking the 2B4 coinhibitory receptor or its ligand, CD48, may reduce mortality during sepsis in humans.
There are approximately 750,000 cases of sepsis annually in the U.S., with up to 370,000 deaths. Currently, there are no approved therapeutics available for the treatment of sepsis if antibiotics and supportive therapy fail. Immune dysregulation can result in immune incompetence, an important mechanism causing mortality during sepsis. Coinhibitory receptors are a class of molecules that can inhibit the survival and function of T cells during an immune response. The blockade of these pathways may represent a potential therapeutic strategy for the treatment of sepsis.
Recent studies have shown that specific immune dysregulation occurs during sepsis. Emory inventors have found that the coinhibitory receptor 2B4 plays a functional role in contributing to immune incompetence and mortality during sepsis. Initial studies indicate that CD4 T-cells from patients with sepsis have elevated 2B4 expression. The inventors have identified 2B4 as a potential target for immunotherapy in sepsis and propose a method of treatment for sepsis by using an antibody against 2B4 or a 2B4-Ig fusion protein to bind to and inactivate CD48.
- Mouse studies have shown that 2B4 knock out mice have increased survival following induction of sepsis.
- Humanized anti-2B4 monoclonal antibodies are in development.