Chimeric Antigen Receptor T Cells Targeting the IgE B Cell Receptor Specifically Eliminate Human IgE Producing B cells

The prevalence of IgE-mediated allergic disorders has risen markedly in industrialized societies, posing significant clinical and socioeconomic challenges. These disorders are characterized by hypersensitivity reactions that range from acute, life-threatening anaphylaxis to chronic conditions such as allergic asthma and autoimmune chronic urticaria. Despite advances in therapeutic strategies, existing treatments—including pharmacological agents, monoclonal antibodies, and immunotherapy—remain limited in their capacity to provide definitive cures. Here, we present a novel chimeric antigen receptor (CAR)-T cell therapy targeting M1’, a unique extracellular domain of the IgE B-cell receptor (BCR). This domain, absent from free IgE, offers an unparalleled opportunity for selective targeting of IgE-producing cells. The CAR construct, derived from the monoclonal antibody Quilizumab, demonstrated robust cytotoxicity against primary human IgE-secreting cells and significantly reduced IgE production in vitro. In an in vivo NSG mouse model, CAR-T cells targeting M1’ inhibited the growth of IgE-expressing tumors and extended survival. By circumventing the limitations of prior CAR designs that target free IgE as well—this strategy provides a novel framework for the development of cellular therapies for allergic diseases. Our findings pave the way for further investigation in transgenic allergy models, with the ultimate goal of clinical translation to offer curative solutions for IgE-mediated disorders.