SLE animal model exhibits key features of disease, highlighting potential of bispecific antibody for B cell targeting.
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease affecting multiple organ systems and is considered one of the most severe autoimmune diseases worldwide, significantly impacting women's health. B cells play a crucial role in disease pathogenesis by becoming abnormally activated and producing autoantibodies that attack the body's normal tissues, leading to inflammation and organ damage. Therefore, targeting the human B cell receptor has emerged as a promising strategy for therapeutic intervention. In this study, we established an SLE animal model using double-humanized CD3/CD19 mice, in which human CD3 and CD19 genes replaced their murine counterparts. The phenotype was confirmed by ELISA and flow cytometry. hCD3/hCD19 mice induced by a combination of pristine x 2, imiquimod (IMQ) and nephrectomy exhibited several key features of SLE, including anti-dsDNA antibody production, proteinuria, increased immune cell populations, and kidney lesions. Furthermore, treatment of these humanized mice with anti-human CD3/CD19 bispecific antibodies significantly inhibited these pathological indicators. Thus, pristine x 2, IMQ and nephrectomy induced hCD3/hCD19 mice provide a validated preclinical model for investigating novel therapeutic agents targeting B cells in SLE.
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Du et al. (2025) studied this question.