B-cell specific duo-conjugates for therapy of autoimmune myasthenia gravis

Abstract

We have prepared a unique set of monoclonal antibody-siRNA conjugates which will target two different subsets of pathogenic B cells in a mouse model of autoimmune myasthenia gravis (EAMG). At the optimum dose, our duo-conjugates significantly reduced two crucial receptors, CD268 and -269, of pathogenic B220 positive cells in PBMCs, lymph node cells and splenocytes in EAMG mice. Modifying the base-composition of the conjugate components further reduced adverse effects of the high dose and significantly decreased pathogenic autoantibody levels, which corresponded with improved clinical symptoms. Our ongoing works suggest a potential for further developing target specific conjugates as highly effective therapeutics for myasthenia gravis.