Dominant CD40 Receptor (CD40R) Antagonist Antibodies as Novel Approach to Treating Autoimmune Diseases

Abstract The CD40R-CD40 ligand pathway is a key co-stimulatory for driving T cell-dependent B cell activation and humoral immune responses. This has been implicated in the pathogenesis of several autoimmune diseases including thyroiditis, type 1 diabetes, Crohn’s disease, inflammatory bowel psoriasis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus Sjogren’s syndrome. Although use anti-CD40 antibodies have shown benefits patients, their linked to development thromboembolic events, ADCC issues low efficacy with poor antagonism vivo. Two novel IgG2 CD40R antagonists developed by BITT differentiated mechanisms action formation inhibitory anti-parallel dimers surface receptor. Several unique features include: independence, Fc receptor potency present selectivity rapidly proliferating cells. Multiple showed strong antagonist activity B-cell proliferation assays. CD40 were selected testing humanized NSG Mouse Model graft verse host disease. compared isotype control known IgG1 antagonist. better depletion inhibition IgG levels – ability selectively deplete activated (CD86+ cells) younger cells making early IgM antibodies. selective could result more potent immune-suppressive function at site inflammation reduced possibility developing side effects.