A Novel Patient-Derived SLE Mouse Model for Non-clinical Evaluation of Novel Therapeutics 4671

Abstract Description Lu Yang1, Juan Liang1 GemPharmatech Co.Ltd., 12 Xuefu Road, Jiangbei New Area, Nanjing, 210061, China1; Systemic Lupus Erythematosus (SLE) is a chronic, relapsing autoimmune disorder where the immune system targets multiple self-nuclear antigens, leading to chronic organ damage and mortality. We developed a novel mouse model for SLE by intraperitoneal injection of SLE patient-derived PBMC into immunodeficient NCG mice. Reconstituted human immune cells can be detected from 2 to 4 weeks post-injection. In addition, certain pathological features of SLE patients can be observed, such as increased anti-dsDNA and total IgG. Although IgG deposition was observed in these mice, no obvious kidney damage was detected possibly due to the short duration of immune reconstitution. Furthermore, we conduct in vivo efficacy studies and demonstrated that B cell-directed therapies, including Bispecific T Cell Engager (BiTE), CAR-T and CAR-NK cells significantly lowered the level of anti-dsDNA, total IgG and kidney deposition of IgG by depleting pathogenic B cells. In summary, we developed and validated a novel patient-derived SLE model that provides a valuable tool to evaluate novel therapeutics to treat SLE. Topic Categories Basic Autoimmunity (BA)