The Nemours Foundation

Zhengyu Ma

A chimeric antigen receptor specific for the extracellular membrane-proximal domain (EMPD) of membrane-bound IgE (mIgE) is provided. The EMPD-specific chimeric antigen receptor comprises an extracellular ligand binding domain capable of binding EMPD, a transmembrane domain, and an intracellular domain that mediates T cell activation upon EMPD binding. Nucleic acids and vectors encoding the EMPD-specific chimeric antigen receptor are provided. T cells transduced with such vectors find use in chimeric antigen receptor-based adoptive T-cell therapy for targeting IgE-expressing B cells and treating IgE-mediated allergic diseases.

Adoptive T-cell therapy using EMPD-specific chimeric antigen receptors for treating IgE-mediated allergic diseases

A chimeric antigen receptor (CAR) contains a human Fc&#x3b5;RI&#x3b1; extracellular domain or a mutant Fc&#x3b5;RI&#x3b1; extracellular domain that has a reduced binding affinity for human IgE compared to wild type human Fc&#x3b5;RI&#x3b1; extracellular domain. The CAR further contains an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). The CAR may further comprise a costimulatory signaling domain, such as an intracellular domain of at least one of the costimulatory molecules 4-1BB, CD27, CD28, CD134 or ICOS. T cells transduced with vectors encoding the CAR are used in CAR-based adoptive T-cell therapy for targeting IgE-expressing B cells and treating IgE-mediated allergic diseases.

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Garnet Valley, PA, United States of America

Zhengyu Ma