Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris

The Journal of Clinical Investigation | August 20, 2020

Desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3 fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B cell depletion. Here, we present definitive preclinical studies enabling a first-in-human trial of DSG3-CAART for mucosal PV. DSG3-CAART specifically lysed human anti-DSG3 B cells from PV patients and demonstrated activity consistent with a threshold dose in vivo, resulting in decreased target cell burden, decreased serum and tissue-bound autoantibodies, and increased DSG3-CAART engraftment.

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Science | July 8, 2016

Autoimmune diseases such as lupus and rheumatoid arthritis lack therapies that specifically target only the disease-causing cells. Inspired by the clinical success of using chimeric antigen receptor T cells to treat certain types of cancers, Ellebrecht et al. asked whether a similar approach might also work against antibody-driven autoimmune diseases.