Expression of a Novel Chimeric Inhibitory Receptor Attenuates CD19 CAR T Cells: A Promising Strategy for Toxicity Mitigation

CAR T cells targeting CD19 are highly effective in patients with refractory/relapsed acute lymphoblastic leukemia and lymphoma but often trigger severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). sCRS occurs when hyperactivated CAR T cells undergo exponential expansion accompanied by the release of excessive amounts of inflammatory cytokines. To mitigate these toxicities, we sought to develop a novel auto-regulatory element in the form of a chimeric inhibitory receptor (CIR), that when engaged by a specific CRS-associated pro-inflammatory molecule will trigger inhibitory signaling within CAR T cells.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 108 Source Type: research