Dörner, T. et al. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res. Ther. 8, R74

Department of Medicine/Rheumatology and Clinical Immunology, Charite Hospital, Berlin, Germany.
Arthritis research & therapy (Impact Factor: 3.75). 04/2006; 8(3):R74. DOI: 10.1186/ar1942
Source: PubMed


B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE), so the safety and activity of anti-B cell immunotherapy with the humanized anti-CD22 antibody epratuzumab was evaluated in SLE patients. An open-label, single-center study of 14 patients with moderately active SLE (total British Isles Lupus Assessment Group (BILAG) score 6 to 12) was conducted. Patients received 360 mg/m2 epratuzumab intravenously every 2 weeks for 4 doses with analgesic/antihistamine premedication (but no steroids) prior to each dose. Evaluations at 6, 10, 18 and 32 weeks (6 months post-treatment) follow-up included safety, SLE activity (BILAG score), blood levels of epratuzumab, B and T cells, immunoglobulins, and human anti-epratuzumab antibody (HAHA) titers. Total BILAG scores decreased by > or = 50% in all 14 patients at some point during the study (including 77% with a > or = 50% decrease at 6 weeks), with 92% having decreases of various amounts continuing to at least 18 weeks (where 38% showed a >/= 50% decrease). Almost all patients (93%) experienced improvements in at least one BILAG B- or C-level disease activity at 6, 10 and 18 weeks. Additionally, 3 patients with multiple BILAG B involvement at baseline had completely resolved all B-level disease activities by 18 weeks. Epratuzumab was well tolerated, with a median infusion time of 32 minutes. Drug serum levels were measurable for at least 4 weeks post-treatment and detectable in most samples at 18 weeks. B cell levels decreased by an average of 35% at 18 weeks and remained depressed at 6 months post-treatment. Changes in routine safety laboratory tests were infrequent and without any consistent pattern, and there was no evidence of immunogenicity or significant changes in T cells, immunoglobulins, or autoantibody levels. In patients with mild to moderate active lupus, 360 mg/m2 epratuzumab was well tolerated, with evidence of clinical improvement after the first infusion and durable clinical benefit across most body systems. As such, multicenter controlled studies are being conducted in broader patient populations.

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Available from: William Wegener, Sep 24, 2015
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    • "In this context, the humanized anti-CD22 monoclonal Ab, Epratuzumab, has been successfully used in the treatment of SLE. It succeeds in depleting 35% of total B cells while managing to inhibit B cell activation and proliferation (87). "
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    ABSTRACT: Transplantation is the preferred treatment for most end-stage solid organ diseases. Despite potent immunosuppressive agents, chronic rejection remains a real problem in transplantation. For many years, the predominant immunological focus of research into transplant rejection has been T cells. The pillar of immunotherapy in clinical practice is T cell-directed, which efficiently prevents acute T cell-mediated allograft rejection. However, the root of late allograft failure is chronic rejection and the humoral arm of the immune response now emerges as an important factor in transplantation. Thus, the potential effects of Abs and B cell infiltrate on transplants have cast B cells as major actors in late graft rejection. Consequently, a number of recent drugs target either B cells or plasma cells. However, immunotherapies, such as the anti-CD20 B cell-depleting antibody, can generate deleterious effects on the transplant, likely due to the deletion of beneficial population. The positive contribution of regulatory B (Breg) cells or B10 cells has been reported in the case of transplantation, mainly in mice models and highlights the primordial role that some populations of B cells can play in graft tolerance. Yet, this regulatory aspect remains poorly characterized in clinical transplantation. Thus, total B cell depletion treatments should be avoided and novel approaches should be considered that manipulate the different B cell subsets. This article provides an overview of the current knowledge on the link between Breg cells and grafts, and reports a number of data advising Breg cells as a new target for future therapeutic approaches.
    Frontiers in Immunology 01/2014; 5:11. DOI:10.3389/fimmu.2014.00011
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    • "Epratuzumab is a novel humanized antihuman CD22 IgG1 monoclonal antibody that binds to the extracellular domain of CD22 and induces modest but significant intracellular phosphorylation. Epratuzumab reduces total blood B cells by about 35–40% and has preferential effects on naïve and transitional B cells [101, 102]. Epratuzumab treatment has been used with moderate clinical success in SLE and primary Sjögren's syndrome [103]. "
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    ABSTRACT: B lymphocytes are the effectors of humoral immunity, providing defense against pathogens through different functions including antibody production. B cells constitute approximately 15% of peripheral blood leukocytes and arise from hemopoietic stem cells in the bone marrow. It is here that their antigen receptors (surface immunoglobulin) are assembled. In the context of autoimmune diseases defined by B and/or T cell autoreactive that upon activation lead to chronic tissue inflammation and often irreversible structural and functional damage, B lymphocytes play an essential role by not only producing autoantibodies but also functioning as antigen-presenting cells (APC) and as a source of cytokines. In this paper, we describe B lymphocyte functions in autoimmunity and autoimmune diseases with a special focus on their abnormalities in systemic lupus erythematosus.
    09/2013; 2013(22):827254. DOI:10.1155/2013/827254
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    • "Promising results have been obtained in a phase II trial for epratuzumab, a humanized anti-CD22 antibody [108,109]. Atacicept, a soluble receptor fusion protein, neutralizes the activity of BLyS and a proliferation-inducing ligand (APRIL) and their heterotrimers [110]. In a phase I trial, atacicept was well tolerated and demonstrated a dose-dependent reduction of immunoglobulin levels and mature/total B cell numbers [111]. "
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