Panorama Research Incorporated — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant Monoclonal antibody for autoimmune disease Abstract B cells play a major role in the pathogenesis of many autoimmune disorders including rheumatoid arthritis RA systemic lupus erythematosus SLE multiple sclerosis and type I diabetes mellitus as indicated by the efficacy of B cell targeted therapies like rituximab in thes diseases Unfortunately current therapies are predicated on B cell depletion which is problematic from a safety standpoint Due to immunosuppression existing standard of care therapies generate adverse effects notably opportunistic infections resulting from long term severe B cell depletion Recently an alternative approach involving the targeting of CD the transducer subunit of the B cell receptor BCR has been described Unlike anti CD mAbs the protective effects of CD targeted mAbs do not require cell depletion rather they act by inducing an unresponsive or anergic state in which B cells physically relocate and are unavailable to participate in immune response generation In the murine MRL lpr model of SLE anti CD antibodies were potently immunosuppressive and effective at decreasing inflammation and improving survival Li In a collagen induced arthritis model of rheumatoid arthritis anti CD antibodies delayed the onset of arthritis and decreased arthritis scores by inducing anergy with transient reversible B cell redistribution Hardy Based on these studies Phase work will identify and characterize a potent anti CD human monoclonal antibody Unlike other B cell targeted biologics that induce B cell death by ADCC complement fixation or survival factor starvation mediated cell death this approach will induce a transient state of polyclonal B cell anergy We expect this second generation immunosuppressive therapeutic to be significantly safer than existing B cell targeted antibodies PUBLIC HEALTH RELEVANCE Autoimmune diseases as a group impose a major health burden While most autoimmune diseases are individually rare in the aggregate they affect of Americans and can be life threatening Current treatments are moderately effective yet carry a heavy risk of adverse effects We have identified a monoclonal antibody specific to B cells which shows efficacy in animal models of rheumatoid arthritis and systemic lupus erythematosus This antibody therapy is safer than competing approaches because its effects are transient and can be quickly reversed if necessary With further development this antibody will greatly improve the therapeutic options for autoimmune diseases