Bispecific antibody targeting IgE-producing B cells for treating allergic diseases

PROJECT SUMMARY/ABSTRACT Severe allergic diseases afflict an increasingly large population and significantly impact the patients’ quality of life. Approximately 25 million Americans suffer from asthma; 5-10% from severe or uncontrolled asthma. Around 32 million Americans have food allergies; 8%, or 5.6 million, are children. An estimated 0.5% to 5% of adults and 1.8% of children live with chronic urticaria. There are currently no cures for severe allergic diseases. High-dose corticosteroids are traditionally used to manage symptoms but are associated with significant side effects. Progresses have been made in oral immunotherapy for peanut allergy, but treatment is not without significant adverse events, and it does not negate continued food avoidance after a five- to nine-month dose escalation course of treatment. While antibodies targeting the key mediator molecule have recently emerged as alternatives, they cannot completely suppress IgE and allergy symptoms for many patients. Therefore, novel approaches that can achieve complete and durable suppression of allergy symptoms is urgently needed. We have developed an innovative antibody drug that has the potential to efficiently and specifically kill B cells that produce IgE without causing significant side effects. In this Phase I project, we propose to determine the potency of the drug in immunocompromised mouse models that are relatively straightforward to establish. Specifically, we will determine the ability of the drug to eliminate IgE-producing human cell lines in cell culture and in NSG mice, and to eliminate IgE-producing primary human B cells in PBMC-NSG mouse models. Data from this project will pave the way for a phase II study that test the potency as well as the toxicity of our antibody drug in more physiological settings, including immunocompetent or humanized mouse models capable of developing allergic symptoms. Our long-term goal is to develop a safe and cost-effective therapy that can achieve complete and long-term suppression of allergic symptoms.