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https://www.readbyqxmd.com/read/27872741/novel-drugs-in-follicular-lymphoma
#1
REVIEW
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
https://www.readbyqxmd.com/read/27663753/biotherapies-in-systemic-lupus-erythematosus-new-targets
#2
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...
September 20, 2016: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/27633749/therapeutic-interventions-of-tissue-specific-autoimmune-onset-in-systemic-lupus-erythematosus
#3
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
https://www.readbyqxmd.com/read/27598855/efficacy-and-safety-of-epratuzumab-in-moderately-to-severely-active-systemic-lupus-erythematosus-results-from-the-phase-3-randomized-double-blind-placebo-controlled-trials-embody%C3%A2-1-and-embody%C3%A2-2
#4
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 B cells. We report data from two Phase 3, randomized, double-blind, placebo-controlled studies of epratuzumab in patients with moderately to severely active SLE; EMBODY 1 (NCT01262365) and EMBODY 2 (NCT01261793). Methods Patients met ≥4 ACR revised criteria, were ANA and/or anti-dsDNA positive, had SLEDAI-2K score ≥6, BILAG-2004 ≥1 A or ≥2 Bs in mucocutaneous, musculoskeletal or cardiorespiratory domains, and were receiving standard therapy (ST) including mandatory corticosteroids (5-60 mg/day)...
September 6, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27521873/new-monoclonal-antibodies-for-the-treatment-of-acute-lymphoblastic-leukemia
#5
REVIEW
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
https://www.readbyqxmd.com/read/27352780/epratuzumab-modulates-b-cell-signaling-without-affecting-b-cell-numbers-or-b-cell-functions-in-a-mouse-model-with-humanized-cd22
#6
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
https://www.readbyqxmd.com/read/27290913/therapeutic-interventions-of-tissue-specific-autoimmune-onset-in-systemic-lupus-erythematosus
#7
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
https://www.readbyqxmd.com/read/27125377/engagement-of-cd22-on-b-cells-with-the-monoclonal-antibody-epratuzumab-stimulates-the-phosphorylation-of-upstream-inhibitory-signals-of-the-b-cell-receptor
#8
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
https://www.readbyqxmd.com/read/26921100/monoclonal-antibodies-and-immune-therapies-for-adult-precursor-b-acute-lymphoblastic-leukemia
#9
REVIEW
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
https://www.readbyqxmd.com/read/26687796/-90-y-labelled-anti-cd22-epratuzumab-tetraxetan-in-adults-with-refractory-or-relapsed-cd22-positive-b-cell-acute-lymphoblastic-leukaemia-a-phase-1-dose-escalation-study
#10
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
https://www.readbyqxmd.com/read/26654227/novel-drug-targets-for-personalized-precision-medicine-in-relapsed-refractory-diffuse-large-b-cell-lymphoma-a-comprehensive-review
#11
REVIEW
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...
2015: Molecular Cancer
https://www.readbyqxmd.com/read/26382733/safety-pharmacokinetics-and-pharmacodynamics-of-epratuzumab-in-japanese-patients-with-moderate-to-severe-systemic-lupus-erythematosus-results-from-a-phase-1-2-randomized-study
#12
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/26316325/long-term-safety-and-efficacy-of-epratuzumab-in-the-treatment-of-moderate-to-severe-systemic-lupus-erythematosus-results-from-an-open-label-extension-study
#13
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/26212727/the-mechanistic-impact-of-cd22-engagement-with-epratuzumab-on-b-cell-function-implications-for-the-treatment-of-systemic-lupus-erythematosus
#14
REVIEW
Thomas Dörner, Anthony Shock, David M Goldenberg, Peter E Lipsky
Epratuzumab is a B-cell-directed non-depleting monoclonal antibody that targets CD22. It is currently being evaluated in two phase 3 clinical trials in patients with systemic lupus erythematosus (SLE), a disease associated with abnormalities in B-cell function and activation. The mechanism of action of epratuzumab involves perturbation of the B-cell receptor (BCR) signalling complex and intensification of the normal inhibitory role of CD22 on the BCR, leading to reduced signalling and diminished activation of B cells...
December 2015: Autoimmunity Reviews
https://www.readbyqxmd.com/read/26183319/epratuzumab-inhibits-the-production-of-the-proinflammatory-cytokines-il-6-and-tnf-%C3%AE-but-not-the-regulatory-cytokine-il-10-by-b-cells-from-healthy-donors-and-sle-patients
#15
Vanessa Fleischer, Julia Sieber, Sarah J Fleischer, Anthony Shock, Guido Heine, Capucine Daridon, Thomas Dörner
INTRODUCTION: Cytokines produced by B cells are believed to play important roles in autoimmune diseases. CD22 targeting by epratuzumab has been demonstrated to inhibit phosphorylation of B cell receptor (BCR) downstream signaling in B cells. It has been shown that other sialoadhesin molecules related to CD22 have immunoregulatory functions; therefore, in the present study, we addressed the role of epratuzumab on the production of key cytokines by B cells of patients with systemic lupus erythematosus (SLE) and of healthy donors (HD)...
2015: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/25732247/re-induction-chemoimmunotherapy-with-epratuzumab-in-relapsed-acute-lymphoblastic-leukemia-all-phase-ii-results-from-children-s-oncology-group-cog-study-advl04p2
#16
Elizabeth A Raetz, Mitchell S Cairo, Michael J Borowitz, Xiaomin Lu, Meenakshi Devidas, Joel M Reid, David M Goldenberg, William A Wegener, Hui Zeng, James A Whitlock, Peter C Adamson, Stephen P Hunger, William L Carroll
BACKGROUND: Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. PROCEDURE: Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m(2)/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block...
July 2015: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/25496332/evaluation-of-epratuzumab-as-a-biologic-therapy-in-systemic-lupus-erythematosus
#17
REVIEW
Vijay Rao, Caroline Gordon
B cells play a key role in the pathogenesis of systemic lupus erythematosus. Some of the current biologic therapies target B cells or B-cell activating factors. Epratuzumab is a humanized monoclonal antibody, which targets CD22 on B cells. This review focuses on the safety and efficacy of epratuzumab in systemic lupus erythematosus based on the information from various published clinical trials and presentations at international meetings. Epratuzumab acts as a B-cell modulator through inhibition of B-cell receptor signaling...
2014: Immunotherapy
https://www.readbyqxmd.com/read/25484055/antibodies-to-watch-in-2015
#18
REVIEW
Janice M Reichert
The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 7 antibody therapeutics (secukinumab, evolocumab, mepolizumab, dinutuximab, nivolumab, blinatumomab, necitumumab) are undergoing a first regulatory review in the EU or US...
2015: MAbs
https://www.readbyqxmd.com/read/25484043/extensive-crosslinking-of-cd22-by-epratuzumab-triggers-bcr-signaling-and-caspase-dependent-apoptosis-in-human-lymphoma-cells
#19
Chien-Hsing Chang, Yang Wang, Pankaj Gupta, David M Goldenberg
Epratuzumab has demonstrated therapeutic activity in patients with non-Hodgkin lymphoma, acute lymphoblastic leukemia, systemic lupus erythematosus, and Sjögren's syndrome, but its mechanism of affecting normal and malignant B cells remains incompletely understood. We reported previously that epratuzumab displayed in vitro cytotoxicity to CD22-expressing Burkitt lymphoma cell lines (Daudi and Ramos) only when immobilized on plates or combined with a crosslinking antibody plus a suboptimal amount of anti-IgM (1 μg/mL)...
2015: MAbs
https://www.readbyqxmd.com/read/25429203/profile-of-epratuzumab-and-its-potential-in-the-treatment-of-systemic-lupus-erythematosus
#20
REVIEW
Hanan Al Rayes, Zahi Touma
Management of systemic lupus erythematosus (SLE) represents a fascinating, emerging field. Research has recently provided us with a better understanding of the immunologic alterations of SLE, leading to the creation of immunomodulatory agents designed to disrupt specific cell targets and pro-inflammatory pathways. Despite the improvement in the prognosis of SLE in the last 50 years with the use of immunosuppressive therapy such as cyclophosphamide and mycophenolate mofetil, cytotoxicity remains a major complication of these medications and the need for more specific targeted immunotherapy is increasing...
2014: Drug Design, Development and Therapy
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