Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that can involve many organ systems [1]. In Europe and the United States, estimates of the number of affected individuals range from 24 to 65 cases per 100,000 people [1,2]. The clinical course of SLE is episodic, with recurring activity flares causing increasing disability and organ damage. Cyclophosphamide, azathoprine, and corticosteroids remain important for long-term management of most patients having active disease, and even those in clinical remission [1]. Despite the important advances made with these drugs, especially cyclophosphamide, in controlling lupus disease activity, they have considerable cytotoxicity and cause, for example, bone marrow depression, ovarian failure, enhanced risk of bladder cancer, as well as the known side effects of long-term systemic corticosteroid therapy. As such, there continues to be a need for the development of targeted and less toxic therapies.Specific autoantibodies against nuclear, cytoplasmic, and membrane antigens remain the serological hallmark of SLE. While lymphopenia is common, there is an increase in the level of activated B cells [3,4] and characteristic alterations of B cell subpopulations [5,6] that may be driven by extrinsic or intrinsic factors. B cells appear to have a key role in the activation of the immune system, in particular through the production of cytokines and by serving as antigen-presenting cells (reviewed recently in [7] ). Although B cell activation can occur independently of T cell help in lupus, a substantial fraction of B cells is activated in a T cell dependent manner [8-10], as demonstrated by isotype switching and affinity maturation of B cells [11,12] and enhanced CD154-CD40 interactions [13]. Useful insight into the pathogenesis of lupus has been obtained with animal models. MRL/lpr mice spontaneously develop a lupus-like autoimmune disease in an age-dependent manner, including autoantibody production, arthritis, skin