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

Department of Medicine/Rheumatology and Clinical Immunology, Charite Hospital, Berlin, Germany.
Arthritis research & therapy (Impact Factor: 4.12). 04/2006; 8(3):R74. DOI: 10.1186/ar1942
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Systemic lupus erythemathosus (SLE) is an autoimmune disease characterized by development of self - reactive B and T cells and autoantibody production. In particular, double-stranded DNA (dsDNA) - specific B cells play important role in lupus progression and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring as a new DNA-based therapy of SLE, a DNA chimeric molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of a FcγRIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The DNA chimeric molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. The intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase of IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile and suppression of lupus nephritis.
    Human Gene Therapy Methods 10/2012; 23(6). DOI:10.1089/hgtb.2012.051 · 1.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many rheumatologic disorders, most notably Sjögren's syndrome, are associated with dental complications and in some cases oral diseases may trigger or drive connective tissue disease. During the past three decades the treatment in rheumatology was revolutionized by the introduction of disease-modifying anti-rheumatic drugs. Advances in our understanding of the pathogenesis of rheumatic diseases have led to the discovery of critical mechanisms of inflammation and autoimmunity and the invention of new target-specific biologic agents. In this review, we will summarize the current state of biologic therapies in rheumatology and discuss the implications of these on oral health and disease.
    Oral Diseases 05/2008; 14(3):206-16. DOI:10.1111/j.1601-0825.2008.01440.x · 2.40 Impact Factor
  • Source

Preview (3 Sources)

1 Download
Available from