Soluble IgE receptor with mutliple functions to reduce inflammation
Lisa Ganley-Leal
Director of Infectious Diseases and Vaccine Development, STC Biologics, Inc.
Approximately 25% (75 million) of the US population suffers from some form of allergy. In general, patients report overall low satisfaction with allergy treatments. The financial burden on health care and significant morbidity associated with allergy warrants the development of new strategies to alleviate disease. Allergy is caused by the immune system’s exaggerated response to harmless antigens, such as pollen and nut allergens. Paradoxically, people who are infected with parasitic worms demonstrate high levels of IgE and activated effector cells, but do not present with classical clinical allergic symptoms seen in Western populations. We have identified a molecule that likely plays an important role in regulating the immune response in a human parasitic disease that prevents classical allergy symptoms. Remarkably, parasitic worms modify a small, 15 kDa soluble IgE binding protein, which we showed sequesters free IgE in an immuno-evasion tactic to promote parasitism. This parasite-modified IgE binding protein therefore represented an ideal mechanism to effectively treat a broad range of allergic conditions in a natural manner that might promote immunological homeostasis. We thus further developed the IgE-binding protein, herein ET523, by inserting a strategic point mutation that allows higher affinity for IgE. We have demonstrated that ET523 also inhibits inflammation and directly blocks granulocyte degranulation extending its potential use into multiple diseases, include cystic fibrosis. The worldwide demand for reliable treatments for allergic diseases is growing. We aim to develop ET523 into a safe and effective drug to treat most allergic diseases in a natural manner with fewer side effects.