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Autosomal Recessive Chronic Granulomatous Disease, IgA Deficiency and Refractory Autoimmune Thrombocytopenia Responding to Anti-CD20 Monoclonal Antibody
Shahin Shamsian Bibi,Davoud Mansouri,Zahra Pourpak,Nima Rezaei
Iranian Journal Of Allergy, Asthma and Immunology , 2008,
Abstract: Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody).Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients.
Rituximab (anti-CD20 monoclonal antibody) in the treatment for refractory pemphigus vulgaris and foliaceus. Rytuksymab (monoklonalne przeciwcia o anty-CD20) w leczeniu opornych na leczenie przypadków p cherzycy zwyk ej i ojotokowej.
Rafa? Bia?ynicki-Birula,0 0
Clinical Dermatology , 2009,
Abstract: This review focused on pemphigus vulgaris (PV) and pemphigus foliaceus (PF) therapy with rituximab. Rituximab, a chimeric monoclonal antibody directed against CD20 of B cells, has been reported to be effective in the treatment of B-cell lymphomas and malignant and nonmalignant plasma cell-dependent diseases. Pemphigus is a severe autoimmune blistering disorder caused by autoantibodies to desmoglein 1 and 3. The disease course is typically severe, potentially fatal prognosis disease, thus requiring multiple immunosuppressive agents. The treatment is still challenging and in some patients with recalcitrant disease therapies fail. It seems logic to use rituximab in the treatment for refractory or severe PV, PF and paraneoplastic pemphigus (PNP). Up to day more than 130 patients with pemphigus vulgaris or foliaceus were treated with rituximab. The majority of patients received one course of rituximab with conventional immunosuppressive therapy as concomitant therapy. Successful rituximab therapy is reported in about 90% of cases. Rituximab is a promising treatment for pemphigus, but a long list of side effects can occur. The future clinical trials with rituximab are necessary to establish the new effective treatment for PV and PF.
Uso del rituximab(anticuerpo monoclonal anti-CD20) en lupus eritematoso sistémico refractario a tratamiento: Caso clínico Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: Report of one case  [cached]
Francisca Sabugo S,Carolina Llanos M,Lilian Soto S,Jorge Gutiérrez
Revista médica de Chile , 2005,
Abstract: New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m2 for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later
Ofatumumab: a novel monoclonal anti-CD20 antibody
Thomas S Lin
Pharmacogenomics and Personalized Medicine , 2010,
Abstract: Thomas S LinGlaxoSmithKline Oncology R&D, Collegeville, PA, USAAbstract: Ofatumumab, a novel humanized monoclonal anti-CD20 antibody, was recently approved by the FDA for the treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL). Ofatumumab effectively induces complement-dependent cytotoxicity (CDC) in vitro, and recent studies demonstrated that ofatumumab also effectively mediates antibody-dependent cellular cytotoxicity (ADCC). Pharmacokinetic studies indicated that increased exposure to the antibody correlated with improved clinical outcome in CLL. Thus, pharmacogenomics may be important in identifying which patients are more likely to respond to ofatumumab therapy, although such studies have not yet been performed. Patients with the high-affinity FCGR3a 158 V/V polymorphism may be more likely to respond to therapy, if ADCC is the primary in vivo mechanism of action of ofatumumab. Patients with increased expression of the complement defense proteins CD55 and CD59 may be less likely to respond if ofatumumab works in vivo primarily via CDC. Patients with increased metabolism and clearance of ofatumumab may have lower exposure and be less likely to respond clinically. Thus, pharmacogenomics may determine the responsiveness of patients to ofatumumab therapy.Keywords: monoclonal antibody, CD20, CLL, NHL, lymphoma
Ofatumumab: a novel monoclonal anti-CD20 antibody
Thomas S Lin
Pharmacogenomics and Personalized Medicine , 2010, DOI: http://dx.doi.org/10.2147/PGPM.S6840
Abstract: tumumab: a novel monoclonal anti-CD20 antibody Review (5213) Total Article Views Authors: Thomas S Lin Published Date May 2010 Volume 2010:3 Pages 51 - 59 DOI: http://dx.doi.org/10.2147/PGPM.S6840 Thomas S Lin GlaxoSmithKline Oncology R&D, Collegeville, PA, USA Abstract: Ofatumumab, a novel humanized monoclonal anti-CD20 antibody, was recently approved by the FDA for the treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL). Ofatumumab effectively induces complement-dependent cytotoxicity (CDC) in vitro, and recent studies demonstrated that ofatumumab also effectively mediates antibody-dependent cellular cytotoxicity (ADCC). Pharmacokinetic studies indicated that increased exposure to the antibody correlated with improved clinical outcome in CLL. Thus, pharmacogenomics may be important in identifying which patients are more likely to respond to ofatumumab therapy, although such studies have not yet been performed. Patients with the high-affinity FCGR3a 158 V/V polymorphism may be more likely to respond to therapy, if ADCC is the primary in vivo mechanism of action of ofatumumab. Patients with increased expression of the complement defense proteins CD55 and CD59 may be less likely to respond if ofatumumab works in vivo primarily via CDC. Patients with increased metabolism and clearance of ofatumumab may have lower exposure and be less likely to respond clinically. Thus, pharmacogenomics may determine the responsiveness of patients to ofatumumab therapy.
Potential therapeutic strategy for non-Hodgkin lymphoma by anti-CD20scFvFc/CD28/CD3zeta gene tranfected T cells
Yihu Zheng, Kang Yu, Jimei Du, Lei Jiang, Shenghui Zhang, Yixiang Han, Panpan Yu, Yingxia Tan
Journal of Experimental & Clinical Cancer Research , 2010, DOI: 10.1186/1756-9966-29-121
Abstract: In this study, we developed a vector construction encoding a chimeric T cell receptor that recognizes the CD20 antigen and delivers co-stimulatory signals to achieve T cell activation. One non-Hodgkin lymphoma cell line Raji cells co-cultured with peripheral blood-derived T cells were stably transfected with anti-CD20scFvFc/CD28/CD3zeta gene or anti-CD20scFvFc gene. T cells expressing anti-CD20scFvFc/CD28/CD3zeta or anti-CD20scFvFc gene co-cultured with CD20 positive Raji cells for different times. Cell lysis assay was carried by [3H]TdR release assay. The expressions of Fas, Bcl-2 and Caspase-3 of Raji cells were detected by flow cytometric. The secretion of IFN-gamma and IL-2 in co-culture medium was tested by ELISA assay. Activity of AP-1 was analyzed by EMSA.Following efficient transduction of peripheral blood-derived T cells with anti-CD20scFvFc/CD28/CD3zeta gene, an obvious cell lysis of Raji cells was observed in co-culture. T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene had superior secretion of IFN-gamma and IL-2 compared to T cells transduced anti-CD20scFvFc gene. Also it led to a much stronger Fas-induced apoptosis signaling transduction in target cancer cells.So adoptively T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene mediates enhanced anti-tumor activities against CD20 positive tumor cells, suggesting a potential of gene-based immunotherapy for non-Hodgkin lymphoma.Non-Hodgkin's lymphoma, known as one of hematologic malignancies, is aggressive tumor with a poor prognosis. Although the clinical outcome of the patients has improved dramatically with combination chemotherapy (CHOP and other standard protocols) and anti-CD20 monoclonal antibody therapy, non-Hodgkin's lymphoma has been proved to be refractory or relapse, and is ultimately failure to standard treatments [1]. Therefore, various strategies have been proposed to treat Non-Hodgkin's lymphoma. Adoptive immunotherapy with genetically modified T cells expressing cTCRs targeting lymphoma
Application of anti-CD20 monoclonal antibodies in the treatment of lymphoproliferative diseases
Pej?i? Ivica,Vrbi? Svetislav
Archive of Oncology , 2009, DOI: 10.2298/aoo0904065p
Abstract: Out of numerous studied monoclonal antibodies, only a few reached the stage of clinical application. The CD20 molecule, non-glycolysed phospholipoprotein (usually termed B1), belonging to the tetraspan (TM4SF) family, 35-37 kD, is characteristic for all mature B lymphocytes, including CLL cells. The CD20 receptors, characteristic for 'B' lymphoproliferative diseases, have been demonstrated to be a good target for therapeutic effects to be achieved. Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody, with the sequences of the human constant region and sequences of the murine variable region. It is specifically bound to the B-lymphocyte CD20 antigen. The mechanism of all rituximab antitumor activity has not been established, but ADCC and CDC are believed to be the principal, with possible complementary effects. Therapeutic use of anti-CD20 monoclonal antibodies has demonstrated a significant benefit in the patients with 'B' CD20 positive lymphoproliferative diseases. Rituximab is today a golden standard for the comparation with other treatment modalities, increasingly in combination with chemotherapy.
The Evolution of Immunotherapy; Looking at Anti-CD20 Monoclonal Antibodies
Megan C Lewicki
University of Toronto Journal of Undergraduate Life Sciences , 2010,
Abstract: Megan C. Lewicki1 1 Second Year Undergraduate Student, Biochemistry and Immunology Major Programs, University of Toronto, Toronto, Ontario Over the past 10 years, immunotherapy has emerged as one of the most promising fields in neoplastic research. Immunotherapy involves introducing an antibody into the blood that recognizes and flags a particular cell marker expressed by malignant cells, allowing the immune system to destroy them. In 1997 the first immunotherapeutic drug, Rituximab, a CD20 monoclonal antibody, was approved by the FDA for treating Non-Hodgkin’s Lymphoma. Since then, Rituximab has become the most commercially successful cancer therapy with sales of over $ 10 billion worldwide. More CD20 therapeutics are now appearing on the market along with many immunotherapies targeting other cancer and autoimmune cell markers. Their popularity and potential for future use comes from their specificity when binding to target cells, leaving most healthy cells untouched. Immunotherapies can also have significantly reduced side effects compared to traditional chemotherapies. Rituximab in particular has enjoyed great success in treating B cell lymphomas, since CD20 is only expressed on early B cells and more differentiated B cells, but not on healthy precursor B cells. More recent CD20 therapies are designed to improve the efficiency of targeted cell death and further decrease side effects. Such an approach is used by the drugs Zevalin and Bexxar, which target CD20 cells with conjugated radioactive isotopes, delivering radiation to specific cells. Another effective strategy is conjugating chemotherapeutic agents to CD20 antibodies to deliver chemotherapy only to target cells. This has already been accomplished for a CD33 antibody, Mylotarg, in treating acute myeloid leukemia. The future prospects for antibody oncology are bright.
A new approach to comparing anti-CD20 antibodies: importance of the lipid rafts in their lytic efficiency
Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, et al
OncoTargets and Therapy , 2010, DOI: http://dx.doi.org/10.2147/OTT.S9774
Abstract: new approach to comparing anti-CD20 antibodies: importance of the lipid rafts in their lytic efficiency Review (3725) Total Article Views Authors: Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, et al Published Date June 2010 Volume 2010:3 Pages 99 - 109 DOI: http://dx.doi.org/10.2147/OTT.S9774 Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, Pierre Youinou, Anne Bordron Centre Hospitalier Universitaire EA2216 and IFR148, Université de Bretagne Occidentale and Université Européenne de Bretagne, BP824, 29609 Brest cedex, France Abstract: The view that B lymphocytes are pathogenic in diverse pathological settings is supported by the efficacy of B-cell-ablative therapy in lymphoproliferative disorders, autoimmune diseases and graft rejection. Anti-B-cell antibodies (Abs) directed against CD20 have therefore been generated, and of these, rituximab was the first anti-CD20 monoclonal Ab (mAb) to be applied. Rituximab-mediated apoptosis, complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity differ from one disease to another, and, for the same disease, from one patient to another. This knowledge has prompted the development of new anti-CD20 mAbs in the hope of improving B-cell depletion. The inclusion of CD20/anti-CD20 complexes in large lipid rafts (LRs) enhances the results of some, but not all, anti-CD20 mAbs, and it may be possible to include smaller LRs. Lipid contents of membrane may be abnormal in malignant B-cells, and could explain resistance to treatment. The function of these mAbs and the importance of LRs warrant further investigation. A detailed understanding of them will increase results for B-cell depletion in lymphoproliferative diseases.
A new approach to comparing anti-CD20 antibodies: importance of the lipid rafts in their lytic efficiency  [cached]
Mariam Hammadi,Jacques-Olivier Pers,Christian Berthou,et al
OncoTargets and Therapy , 2010,
Abstract: Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, Pierre Youinou, Anne BordronCentre Hospitalier Universitaire EA2216 and IFR148, Université de Bretagne Occidentale and Université Européenne de Bretagne, BP824, 29609 Brest cedex, FranceAbstract: The view that B lymphocytes are pathogenic in diverse pathological settings is supported by the efficacy of B-cell-ablative therapy in lymphoproliferative disorders, autoimmune diseases and graft rejection. Anti-B-cell antibodies (Abs) directed against CD20 have therefore been generated, and of these, rituximab was the first anti-CD20 monoclonal Ab (mAb) to be applied. Rituximab-mediated apoptosis, complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity differ from one disease to another, and, for the same disease, from one patient to another. This knowledge has prompted the development of new anti-CD20 mAbs in the hope of improving B-cell depletion. The inclusion of CD20/anti-CD20 complexes in large lipid rafts (LRs) enhances the results of some, but not all, anti-CD20 mAbs, and it may be possible to include smaller LRs. Lipid contents of membrane may be abnormal in malignant B-cells, and could explain resistance to treatment. The function of these mAbs and the importance of LRs warrant further investigation. A detailed understanding of them will increase results for B-cell depletion in lymphoproliferative diseases.Keywords: anti-CD20 antibodies, lymphocyte B, lipid rafts, B-cell disorders
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