Posted by Adam Awdish on
Yuki Imura, Makoto Ando, Taisuke Kondo, Minako Ito, and Akihiko Yoshimura
July 23, 2020
Tregs suppress excess immunity responses against a variety of antigens, including self-antigens, bacteria–derived antigens, and environmental allergens. Thus, Tregs have been shown to play important roles in suppressing the development of allergies. In humans, some clinical trials of transfer of ex vivo expanded polyclonal Tregs have been performed to suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation and type 1 diabetes (T1D). Although the results of polyclonal Treg adoptive therapy are encouraging, many cells are necessary, and the risk of nonspecific immunosuppression should be considered. There are several strategies to generate antigen-specific Tregs, which indicate superior suppression of nonspecific or polyclonal Tregs for several diseases. In mice, in vitro generation of induced antigen-specific Tregs (iTregs) have been used to suppress GvHD, but methods for generating stabilized human iTregs have not yet been established. One way to create antigen-specific T cells is through chimeric antigen receptor (CAR) expression, which consists of an extracellular single chain antibody (scFv) fused to intracellular signaling domains in primary T cells. These CAR T cells have been successfully used in cancer treatment and are approved for treatment of patients with certain types of B cell lymphoma. CAR therapy is a way to facilitate interaction of Tregs with target cells and may be safer than conventional CAR T cells because of the low inflammatory effects and cytotoxicity of Tregs. Autoantibodies secreted from B cells are thought to induce various autoimmune diseases and IgG4-related diseases. Although one report used conventional CD19-targeted CAR (CD19-CAR) CD8+ T cells for the treatment of SLE in murine SLE models, there are no reports on the application of CD19-CAR Tregs for autoimmune B cell control. In this study, researchers demonstrated that CD19-CAR Tregs suppress the antibody production of B cells without harmful side effects such as GvHD. The adoptive transfer of CD19-CAR Tregs might provide a novel therapeutic method to treat autoantibody-mediated autoimmune diseases. Pooled Human AB Serum Plasma Derived from Innovative Research was used in this study.
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