Artificial Immune Receptors as novel tools to engineer inflammation sensing regulatory T cells for cell therapy

Engineered regulatory T cell (Treg) therapy is a promising strategy to treat patients suffering from inflammatory diseases and autoimmunity. In this study, we introduce a new class of synthetic sensors, named Artificial Immune Receptors (AIRs), for murine and human Treg cells that provide new features to this cell type. AIRs bind inflammatory ligands of the TNF-receptor superfamily and translate this environmental signal into a T cell receptor (TCR)-like program, leading to activation and proliferation of the Treg cells. In a preclinical graft-versus-host-disease model, AIR-Treg cells recognizing lymphotoxin-beta-receptor ligands protect significantly better than Treg cells with only a natural TCR repertoire. Expression and signaling of a human AIR construct in human Treg cells prove that the concept can be translated. Inflammation sensing AIR-Treg cells could be an off-the-shelf Treg cell therapy approach without the knowledge of a specific antigen driving the inflammatory process. murine regulatory T-cells were cultured with anti-CD3/CD28 stimulation and IL2 for 2 days,then transduced with MSCV retroviral vector containing ORFS for anti-CD19 CAR as control or DR3,LTBR or TNFR2 AIR.