CAR19 EngTregs offer broad capacity to modulate immune tolerance and improve safety in B and T cell mediated autoimmune disorders 3850
Year: 2025
Type: conference-abstract
Abstract: Description CD19 CAR T-effector (CAR19Teff) therapy is promising in autoimmunity but limited by the inability to modulate pathogenic T cells and safety concerns like cytokine release syndrome and neurotoxicity. To address these limitations, we developed CD19 CAR engineered regulatory T cells (CAR19 EngTregs), which offer B cell depletion with the crucial capacity to suppress pathogenic T cells via bystander suppression and lower inflammatory cytokine secretion. We engineered human CAR19 EngTregs with stable FOXP3 and CAR expression and enriched edited cells to high purity using a chemically induced IL-2 signaling complex (CISC). CAR19 EngTregs exhibited stable core Treg markers upon CAR or TCR stimulation and mediated robust T cell suppression. In a human plasma B cell generation assay, CAR19 EngTregs showed antigen-dependent activation, and prevented B cell proliferation, differentiation to plasmablasts and long-lived plasma cells, and immunoglobulin (Ig) production. In both in vitro killing assays and adoptive transfer studies in humanized mice, CAR19 EngTregs mediated B cell depletion with lower cytotoxic and inflammatory cytokine levels than CAR19Teff. In pristane-treated humanized mice, human CAR19 EngTregs depleted B cells in vivo, elicited lower serum inflammatory cytokines, lower Ig titers, and reduced pathology versus CAR19Teff. These data demonstrate CAR19 EngTreg therapy could treat B and T cell-mediated autoimmunity with superior efficacy and safety than CAR19Teff therapy. Topic Categories Therapeutic Approaches to Autoimmunity (THER)
Source: The Journal of Immunology
Authors: Victoria L. DeVault, Matteo Doglio, Annaiz Grimm, Jennifer Mellen Mellen, Pierluigi Carulli, Peter Cook, Payam Zarin, Maegan Hoover, Tingxi Guo, Chris Moore, Barbara Camisa, Clara Bercher, Alessia Ugolini, Francesca Sanvito, Patrizia Cristofori, Travis Drow, Brock McKinney, Noelle Dahl, Aesha Vakil, Brian Christin, Gene Uenishi, Chandra Patel, Tiffany Chen, David Rawlings, Chiara Bonini, Tom Wickham, Alberto Del Rio-Espinola
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416449244
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