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Hind Letaief, Cédric Lukas, Thomas Barnetche, Cécile Gaujoux-Viala, Bernard Combe, Jacques Morel
OBJECTIVE: In this review, we summarise the clinical efficacy and safety of B-Cell Targeted therapies for primary Sjögren's syndrome (pSS). METHODS: A systematic literature review was conducted using databases including MEDLINE, EMBASE and Cochrane. Only articles reporting controlled or prospective studies of b-DMARDs modulating B cells in treatment of pSS were selected. The highest-quality studies were selected for meta-analysis. The primary outcome of interest was clinical efficacy at week 24 on fatigue, dryness, Schirmer test, salivary flow rate and the full ESSDAI score including biological domain...
June 30, 2017: Joint, Bone, Spine: Revue du Rhumatisme
Tatyana A Shamliyan, Paula Dospinescu
PURPOSE: The role of biologic disease-modifying drugs in patients with systemic lupus erythematosus (SLE) remains controversial. METHODS: Following systematic review and meta-analysis protocol, we searched PubMed, EMBASE, Cochrane Library, and in January 2017 to identify all studies of people with SLE treated with biologic response modifiers. We performed direct frequentist random effects meta-analyses, calculated pooled relative risk and number needed to treat to achieve an outcome in 1 patient (NNT) as reciprocal to statistically significant absolute risk difference, and graded the quality of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation criteria...
June 30, 2017: Clinical Therapeutics
Natalia V Giltiay, Geraldine L Shu, Anthony Shock, Edward A Clark
BACKGROUND: Abnormal B-cell activation is implicated in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell surface molecule CD22, which regulates activation through the B-cell receptor (BCR), is a potential target for inhibiting pathogenic B cells; however, the regulatory functions of CD22 remain poorly understood. In this study, we determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22 IgG1 monoclonal antibody, affects the activation of human B-cell subsets in response to Toll-like receptor 7 (TLR7) and BCR engagement...
May 15, 2017: Arthritis Research & Therapy
Chi Chiu Mok
Systemic lupus erythematosus (SLE) is a multi-systemic disease characterized by an unpredictable disease course and periods of remission and flare, leading to organ damage and mortality. Novel biological agents are being developed (targeting the lymphocytes, accessory molecules and cytokines) that aim to enhance the therapeutic efficacy when combined with standard therapies. Areas covered: This article updates recent data on the use of biological and targeted therapies in SLE. Expert commentary: B cells remain the main target of development of novel therapeutics in SLE...
May 5, 2017: Expert Review of Clinical Immunology
Patrice Chevallier, Sylvain Chantepie, Francoise Huguet, Emmanuel Raffoux, Xavier Thomas, Thibaut Leguay, Tony Marchand, Francoise Isnard, Aude Charbonnier, Sébastien Maury, Maria-Pilar Gallego-Hernanz, Nelly Robillard, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Fanny Rialland, Claire Le Houerou, David M Goldenberg, William A Wegener, Marie-C Béné, Hervé Dombret
No abstract text is available yet for this article.
May 2017: Haematologica
Raffaella Franca, Diego Favretto, Marilena Granzotto, Giuliana Decorti, Marco Rabusin, Gabriele Stocco
BACKGROUND: More than 85% of children affected by acute lymphoblastic leukemia (ALL) are successfully treated; however relapse remains a remarkable clinical concern, with 50-60% of relapsing patients facing a fatal outcome. Management of relapsed patients includes standardized intensive risk-adapted regimens based on conventional drugs, and hematopoietic stem cells transplantation for patients with unfavourable features. Biological drugs, in particular the monoclonal antibody epratuzumab and the bi-functional recombinant single chain peptide blinatumomab, have been recently recognized as novel potential agents to be integrated in salvage ALL therapy to further improve rescue outcome...
January 12, 2017: Current Medicinal Chemistry
Françoise Kraeber-Bodere, Amandine Pallardy, Hervé Maisonneuve, Loïc Campion, Anne Moreau, Isabelle Soubeyran, Steven Le Gouill, Olivier Tournilhac, Etienne Daguindau, Henry Jardel, Nadine Morineau, Krimo Bouabdallah, Emmanuel Gyan, Marie-Pierre Moles, Remy Gressin, Christian Berthou, Sophie Sadot, Philippe Moreau, Bénédicte Deau, Caroline Bodet-Milin, Anne-Laure Cazeau, Etienne Garin, Pierre-Yves Salaun, Jean-Philippe Vuillez, Valérie Gouilleux-Gruart, Jacques Barbet, William A Wegener, David M Goldenberg, Thierry Lamy, Pierre Soubeyran
BACKGROUND: Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 (90)Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals...
January 2017: Lancet Haematology
Antonella Anastasia, Giuseppe Rossi
Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of achieving a definite cure, have prompted investigations into the possible role of more active and less toxic strategies with innovative therapeutic agents. Recently Casulo et al. demonstrated that approximately 20% of patients with FL relapse within two years after achieving remission with R-CHOP and have a poor prognosis...
2016: Mediterranean Journal of Hematology and Infectious Diseases
Estibaliz Lazaro, Marc Scherlinger, Marie-Elise Truchetet, Laurent Chiche, Thierry Schaeverbeke, Patrick Blanco, Christophe Richez
Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab - a monoclonal antibody against BLyS (B-lymphocyte stimulator) - to become the first biotherapy approved for use in SLE...
May 2017: Joint, Bone, Spine: Revue du Rhumatisme
Subhajit Dasgupta
Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The auto reactive B cells and T helper cells together are known to develop self-reactive immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy...
September 12, 2016: Mini Reviews in Medicinal Chemistry
Megan E B Clowse, Daniel J Wallace, Richard A Furie, Michelle A Petri, Marilyn C Pike, Piotr Leszczyński, C Michael Neuwelt, Kathryn Hobbs, Mauro Keiserman, Liliana Duca, Kenneth C Kalunian, Catrinel Galateanu, Sabine Bongardt, Christian Stach, Carolyn Beaudot, Brian Kilgallen, Caroline Gordon
OBJECTIVE: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day)...
February 2017: Arthritis & Rheumatology
Nosha Farhadfar, Mark R Litzow
Monoclonal antibodies represent a major advance in treatment of acute lymphoblastic leukemia (ALL). Targeted delivery of these agents based on leukemic cell-surface receptor recognition, improves efficacy and minimizes off-target toxicity. The antigens CD19, CD20, CD22 and CD52, are the most common antigens to which monoclonal antibodies in B-cell ALL have been directed. Rituximab, an anti-CD20 antibody, in combination with conventional chemotherapy has been shown to improve survival in newly diagnosed CD20 positive B-cell ALL...
October 2016: Leukemia Research
Lamia Özgör, Carolin Brandl, Anthony Shock, Lars Nitschke
Treatment of systemic lupus erythematosus patients with epratuzumab (Emab), a humanized monoclonal antibody targeting CD22, leads to moderately reduced B-cell numbers but does not completely deplete B cells. Emab appears to induce immunomodulation of B cells, but the exact mode of action has not been defined. In the present study, we aimed to understand the effects of Emab on B cells using a humanized mouse model (Huki CD22), in which the B cells express human instead of murine CD22. Emab administration to Huki CD22 mice results in rapid and long-lasting CD22 internalization...
September 2016: European Journal of Immunology
Subhajit Dasgupta
Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The auto reactive B cells and T helper cells together are known to develop self-reactive immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy...
June 10, 2016: Mini Reviews in Medicinal Chemistry
Simon Lumb, Sarah J Fleischer, Annika Wiedemann, Capucine Daridon, Alison Maloney, Anthony Shock, Thomas Dörner
The binding of antigen to the B cell receptor (BCR) results in a cascade of signalling events that ultimately drive B cell activation. Uncontrolled B cell activation is regulated by negative feedback loops that involve inhibitory co-receptors such as CD22 and CD32B that exert their functions following phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). The CD22-targeted antibody epratuzumab has previously been shown to inhibit BCR-driven signalling events, but its effects on ITIM phosphorylation of CD22 and CD32B have not been properly evaluated...
June 2016: Journal of Cell Communication and Signaling
Swati Sikaria, Ibrahim Aldoss, Mojtaba Akhtari
Adult B-acute lymphoblastic leukemia (B-ALL) does not share the favorable prognosis seen in pediatric patients with the same disease. Less than 50% of patients experience long-term survival and for those adults over age 60, long-term survival is only 10%. At time of relapse, 5-year prognosis is a dismal 7%. Novel and less toxic agents are urgently needed. The last few years have seen a surge in immune therapies for B-ALL. These agents may target CD19, CD20, CD22, and less frequently CD52. Expression of these surface markers and the drugs which target them are discussed...
April 2016: Immunology Letters
Patrice Chevallier, Thomas Eugene, Nelly Robillard, Françoise Isnard, Franck Nicolini, Martine Escoffre-Barbe, Françoise Huguet, Mathilde Hunault, Antoine Marcais, Joelle Gaschet, Michel Cherel, Thierry Guillaume, Jacques Delaunay, Pierre Peterlin, Marion Eveillard, Xavier Thomas, Norbert Ifrah, Simona Lapusan, Caroline Bodet-Milin, Jacques Barbet, Alain Faivre-Chauvet, Ludovic Ferrer, Marie C Bene, Claire Le Houerou, David M Goldenberg, William A Wegener, Françoise Kraeber-Bodéré
BACKGROUND: Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study. METHODS: Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France...
March 2015: Lancet Haematology
Rosalba Camicia, Hans C Winkler, Paul O Hassa
Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular subtypes of DLBCL: a germinal center B cell-like subtype, an activated B cell-like subtype, and a primary mediastinal B-cell lymphoma subtype...
December 11, 2015: Molecular Cancer
Tomomi Tsuru, Yoshiya Tanaka, Mitsumasa Kishimoto, Kazuyoshi Saito, Seiji Yoshizawa, Yoshinari Takasaki, Tomoya Miyamura, Hiroaki Niiro, Shinji Morimoto, Junichi Yamamoto, Rocio Lledo-Garcia, Jing Shao, Shuichiro Tatematsu, Osamu Togo, Takao Koike
OBJECTIVES: This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care. METHODS: Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period...
2016: Modern Rheumatology
D J Wallace, K Hobbs, M E B Clowse, M Petri, V Strand, M Pike, J T Merrill, P Leszczyński, C M Neuwelt, S Jeka, F Houssiau, M Keiserman, J Ordi-Ros, S Bongardt, B Kilgallen, C Galateanu, K Kalunian, R Furie, C Gordon
OBJECTIVE: The primary objective was to assess the long-term safety of repeated courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL). METHODS: Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care...
April 2016: Arthritis Care & Research
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