Adoptive t-cell therapy using FcεRI-based chimeric antigen receptors for treating IgE-mediated allergic diseases
Abstract:
A chimeric antigen receptor (CAR) contains a human FcεRIα extracellular domain or a mutant FcεRIα extracellular domain that has a reduced binding affinity for human IgE compared to wild type human FcεRIα 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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