The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Beda M. Stadler - One of the best experts on this subject based on the ideXlab platform.
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DARPins against a functional IgE epitope.
Immunology letters, 2010Co-Authors: Michael J. Baumann, Beda M. Stadler, Alexander Eggel, Patrick Amstutz, Monique VogelAbstract:The Monoclonal Anti-IgE antibody omalizumab (Xolair is mostly used for the treatment of severe allergic asthma. However, the requirement of high doses and suboptimal cost-effectiveness limits the use of the treatment. Here we propose to use a new drug format based on non-immunoglobulin structures, potentially offering increased clinical efficacy while being more cost-effective. For this purpose, DARPins™ (designed ankyrin repeat proteins) against the constant heavy chain region of IgE have been isolated. DARPins were binding to IgE with high specificity and affinities in the low nanomolar range. Selected DARPins antagonized the interaction between IgE and its high-affinity receptor in inhibition assays. Furthermore, Anti-IgE DARPins were shown to inhibit proinflammatory mediator release from rat basophilic leukemia cells expressing human high-affinity IgE receptors with higher efficacy than the Monoclonal Anti-IgE antibody omalizumab. DARPins may thus represent promising future drug candidates for the treatment of allergy.
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A highly conserved interspecies V(H) in the human genome.
Journal of molecular biology, 2004Co-Authors: Monique Vogel, Sylvia Miescher, Michael B. Stadler, Cornelia Tschopp, Tomasz Bobrzynski, Michaela Fux, Beda M. StadlerAbstract:Idiotype conservation between human and mouse antibodies has been observed in association with various infectious and autoimmune diseases. We have isolated a human anti-idiotypic antibody to a mouse Monoclonal Anti-IgE antibody (BSW17) suggesting a conserved interspecies idiotype associated with an Anti-IgE response. To find the homologue of BSW17 in the human genome we applied the guided selection strategy. Combining V(H) of BSW17 with a human V(L) repertoire resulted in three light chains. The three V(L) chains were then combined with a human V(H) repertoire resulting in three clones specific for human IgE. Surprisingly, one clone, Hu41, had the same epitope specificity and functional in vitro activity as BSW17 and V(H) complementarity-determining regions identical with that of BSW17. Real-time PCR analysis confirmed the presence of the Hu41 V(H) sequence in the human genome. These data document the first example of the isolation of a human antibody where high sequence similarity to the original murine V(H) sequence is associated with common antigen and epitope specificity.
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Molecular Basis for Nonanaphylactogenicity of a Monoclonal Anti-IgE Antibody
Journal of immunology (Baltimore Md. : 1950), 2000Co-Authors: Michael P. Rudolf, Beda M. Stadler, Monique Vogel, Adrian W. Zuercher, Andreas Nechansky, Christine Ruf, Sylvia Miescher, Franz KricekAbstract:IgE Abs mediate allergic responses by binding to specific high affinity receptors (FcepsilonRI) on mast cells and basophils. Therefore, the IgE/FcepsilonRI interaction is a target for clinical intervention in allergic disease. An Anti-IgE mAb, termed BSW17, is nonanaphylactogenic, although recognizing IgE bound to FcepsilonRI, and interferes with binding of IgE to FcepsilonRI. Thus, BSW17 represents a candidate Ab for treatment of IgE-mediated disorders. By panning BSW17 against random peptide libraries displayed on phages, we defined mimotopes that mimic the conformational epitope recognized on human IgE. Two types of mimotopes, one within the Cepsilon3 and one within the Cepsilon4 domain, were identified, indicating that this mAb may recognize either a large conformational epitope or eventually two distinct epitopes on IgE. On the basis of alignments of the two mimotopes with the human IgE sequence, we postulate that binding of BSW17 to the Cepsilon3 region predominantly blocks binding of IgE to FcepsilonRI, leading to neutralization of IgE. Moreover, binding of BSW17 to the Cepsilon4 region may explain how BSW17 recognizes FcepsilonRI-bound IgE, and binding to this region may also interfere with degranulation of IgE sensitized cells (basophils and mast cells). As a practical application of these findings, mimotope peptides coupled to a carrier protein may be used for the development of a peptide-based anti-allergy vaccine by induction of Anti-IgE Abs similar to the current approach of using humanized nonanaphylactogenic Anti-IgE Abs as a passive vaccine.
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Oral Anti-IgE immunization with epitope-displaying phage.
European journal of immunology, 2000Co-Authors: Adrian W. Zuercher, Monique Vogel, Michael P. Rudolf, Sylvia Miescher, Michael B. Stadler, Beda M. StadlerAbstract:An essential requirement for oral vaccines is the ability to survive the harsh environment of the stomach in an antigenically intact form. As bacteriophages are adapted to this environment we used epitope-displaying M13 bacteriophages as carriers for an experimental oral Anti-IgE vaccine. The feasibility of this approach was tested in a simulated gastric fluid using two different mimotopes as well as an anti-idiotypic Fab of the non-anaphylactogenic Monoclonal Anti-IgE antibody BSW17. All phage clones remained infective after this treatment. However, only epitopes displayed on the pVIII protein were still recognized by BSW17 whereas pIII-expressed epitopes were rapidly inactivated. Surprisingly, when used for oral immunization of mice all phage clones induced Anti-IgE antibodies. In contrast, oral immunization with the purified, pVIII protein displaying the mimotope induced anti-phage but no Anti-IgE antibodies. After feeding a single dose of mimotope-displaying bacteriophage, phage DNA could be detected in mouse feces for 10 days. Our results show that epitope-displaying bacteriophages can be used to induce an epitope-specific antibody response via the oral route.
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Mimotope and Anti–Idiotypic Vaccines to Induce an Anti–IgE Response
International archives of allergy and immunology, 1999Co-Authors: Beda M. Stadler, Sylvia Miescher, Franz Kricek, Adrian W. Zürcher, Monique VogelAbstract:We have defined epitopes on human IgE by screening different phage display random peptide libraries with a Monoclonal anti–IgE antibody termed BSW17. The selected mimotopes and epitopes within the Ce3 and Ce4 region of IgE induced antibodies that were nonanaphylactogenic and had biological activity similar to BSW17. The chemically synthesized and KLH–coupled IgE epitopes or mimotopes were used to induce an anti–IgE response in rhesus monkeys. The immunized rhesus monkeys were subsequently protected in a PCA test when sensitized with human IgE and triggered with the corresponding allergen. Furthermore, using the same Monoclonal anti–IgE antibody, we also generated an anti–idiotypic antibody that showed sequence homology with the IgE epitope in the Ce3 domain. This anti–idiotypic antibody as well as the mimotopes were then used in a mouse model to induce orally an anti–IgE immune response. For this purpose mice were fed by intragastric gavages with bacteriophages displaying the small IgE–homologous structures. Orally immunized mice produced serum anti–IgE antibodies that were inhibited by BSW17 suggesting that it may be possible to induce a systemic anti–IgE response orally.
Serge Doan - One of the best experts on this subject based on the ideXlab platform.
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Experience with the Monoclonal anti IgE antibody Omalizumab in severe refractory vernal keratoconjunctivitis in children
Acta Ophthalmologica, 2015Co-Authors: Serge Doan, F. Amat, Eric E. Gabison, J. Just, Isabelle CochereauAbstract:Purpose Vernal keratoconjunctivis (VKC) is a severe form of pediatric ocular allergy, characterized by acute and chronic corneoconjunctival inflammation that may lead to visual sequelae. Although topical cyclosporine is usually effective, severe forms may be refractory and require prolonged steroid therapy. Omalizumab is a Monoclonal anti IgE antibody, administered systematically and authorized for severe asthma. We report our clinical experience with omalizumab in severe VKC children. Methods We retrospectively reviewed the files of 4 boys treated with omalizumab because of severe VKC, defined as persistent corneal inflammation despite continuous topical 2% cyclosporine and steroid eye drops. Results Four boys, aged 7 to 13 years old, were treated. All children had asthma and 1 had severe lid eczema. Two patients had required supratarsal steroid injections. Omalizumab was administered every 2 weeks by subcutaneous injections, at doses varying from 450 to 600 mg per injection. Three patients out of 4 responded to the treatment, with a decrease in frequency and in duration of the inflammatory flares, and also a decreased need for topical steroid. However, the response was incomplete and they still had inflammatory corneoconjunctival flares despite continuous topical cyclosporine. On the other hand, asthma and lid eczema were completely controlled in these 3 patients. The fourth child did not respond to o and needed oral steroids for his VKC and his asthma. Noticeably, this patient did not have detectable sensitization to any allergen, contrary to the other cases. The treatment was stopped in this refractory case, but is still ongoing in all other cases, with a median duration of 16 months (6 to 26 months). Conclusions Omalizumab is an interesting treatment in severe refractory forms of VKC, but its efficacy is incomplete in these very severe cases.
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IgE, anti‐IgE, and allergic keratoconjunctivitis ‐ part 1
Acta Ophthalmologica, 2014Co-Authors: Serge DoanAbstract:Vernal and atopic keratoconjunctivis (VKC, AKC) are severe types of ocular allergy, characterized by acute and chronic corneoconjunctival inflammation that may lead to visual sequelae. Although topical immunosuppressive drugs such as cyclosporine and tacrolimus are usually effective, some severe may be refractory. Omalizumab is a Monoclonal anti IgE antibody, administered systematically and authorized for severe asthma. We will report our clinical experience of omalizumab in AKC and VKC patients, and will also detail a review of the literature.
Rosario Maselli - One of the best experts on this subject based on the ideXlab platform.
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Asthma: Targeted Biological Therapies
2017Co-Authors: Girolamo Pelaia, Alessandro Vatrella, Rosario MaselliAbstract:This book focuses on the fundamentals of the use of biologics in asthma, describing the rationale, principles, mechanisms of action, and indications. It offers an excellent balance between basic science and the analysis of clinical trials, updating readers with new developments that are changing the global scenario for targeted biological anti-asthma therapies, especially with regard to more severe disease. A range of therapies are considered, from the humanized Monoclonal Anti-IgE antibody omalizumab, widely approved as add-on treatment for inadequately controlled disease, through to emerging biologics for which evidence supportive of efficacy is accumulating, including anti-IL-5, anti-IL-4, and anti-IL-13 therapies. One aspect to emerge is the variability in individual response, which suggests a need for characterization of different asthma subtypes to permit the effective implementation of phenotype-targeted treatments. This book will be of interest for pulmonologists, clinical immunologists, and physicians seeking sound information on these therapies, but also for scientists and pharmacologists wishing to enhance their knowledge of the therapeutic implications of the cellular and molecular mechanisms that underlie severe, uncontrolled asthma
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Anti-IgE therapy with omalizumab for severe asthma: current concepts and potential developments.
Current drug targets, 2015Co-Authors: Girolamo Pelaia, Luca Gallelli, Maria Teresa Busceti, Alessandro Vatrella, Rosa Terracciano, Rosario MaselliAbstract:The humanized Monoclonal Anti-IgE antibody omalizumab is currently the only biologic drug approved for asthma treatment. Omalizumab inhibits allergic responses by binding to serum immunoglobulins E (IgE), thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of down-regulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both peripheral blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Moreover, some recent studies suggest potential benefits of omalizumab also in non allergic phenotypes of severe asthma. Very interesting are also further recent reports referring to the potential inhibitory effect of omalizumab with regard to bronchial structural changes, especially occurring in severe asthma and globally defined as airway remodeling. Omalizumab is relatively well tolerated, and only very rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent asthma, inadequately controlled by high doses of standard inhaled treatments.
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An insight into pharmacological and clinical basis of Anti-IgE for add-on therapy of severe asthma
Shortness of Breath, 2013Co-Authors: Girolamo Pelaia, Luca Gallelli, Maria Teresa Busceti, Alessandro Vatrella, Rosario MaselliAbstract:IgE antibodies are crucially involved in mediating, maintaining and amplifying the allergic cascade. The humanized Monoclonal Anti-IgE antibody omalizumab is currently the only biologic drug approved for asthma treatment. Anti-IgE inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of down-regulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both peripheral blood and induced sputum. Randomized clinical trials showed relevant clinical effects of omalizumab including improvements of respiratory symptoms and quality of life. Moreover, a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators was also observed. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for most severe patients with persistent allergic asthma, inadequately controlled by high doses of standard treatments.
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Update on optimal use of omalizumab in management of asthma.
Journal of asthma and allergy, 2011Co-Authors: Girolamo Pelaia, Luca Gallelli, Teresa Renda, Pasquale Romeo, Maria Teresa Busceti, Rosa Daniela Grembiale, Rosario Maselli, Serafino A. Marsico, Alessandro VatrellaAbstract:Omalizumab is a humanized Monoclonal Anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.
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Review: Omalizumab in the treatment of severe asthma: efficacy and current problems:
Therapeutic advances in respiratory disease, 2008Co-Authors: Girolamo Pelaia, Teresa Renda, Pasquale Romeo, Maria Teresa Busceti, Rosario MaselliAbstract:Omalizumab is a humanized Monoclonal Anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high-affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma, inadequately controlled by high doses of standard inhaled treatments.
Monique Vogel - One of the best experts on this subject based on the ideXlab platform.
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DARPins against a functional IgE epitope.
Immunology letters, 2010Co-Authors: Michael J. Baumann, Beda M. Stadler, Alexander Eggel, Patrick Amstutz, Monique VogelAbstract:The Monoclonal Anti-IgE antibody omalizumab (Xolair is mostly used for the treatment of severe allergic asthma. However, the requirement of high doses and suboptimal cost-effectiveness limits the use of the treatment. Here we propose to use a new drug format based on non-immunoglobulin structures, potentially offering increased clinical efficacy while being more cost-effective. For this purpose, DARPins™ (designed ankyrin repeat proteins) against the constant heavy chain region of IgE have been isolated. DARPins were binding to IgE with high specificity and affinities in the low nanomolar range. Selected DARPins antagonized the interaction between IgE and its high-affinity receptor in inhibition assays. Furthermore, Anti-IgE DARPins were shown to inhibit proinflammatory mediator release from rat basophilic leukemia cells expressing human high-affinity IgE receptors with higher efficacy than the Monoclonal Anti-IgE antibody omalizumab. DARPins may thus represent promising future drug candidates for the treatment of allergy.
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A highly conserved interspecies V(H) in the human genome.
Journal of molecular biology, 2004Co-Authors: Monique Vogel, Sylvia Miescher, Michael B. Stadler, Cornelia Tschopp, Tomasz Bobrzynski, Michaela Fux, Beda M. StadlerAbstract:Idiotype conservation between human and mouse antibodies has been observed in association with various infectious and autoimmune diseases. We have isolated a human anti-idiotypic antibody to a mouse Monoclonal Anti-IgE antibody (BSW17) suggesting a conserved interspecies idiotype associated with an Anti-IgE response. To find the homologue of BSW17 in the human genome we applied the guided selection strategy. Combining V(H) of BSW17 with a human V(L) repertoire resulted in three light chains. The three V(L) chains were then combined with a human V(H) repertoire resulting in three clones specific for human IgE. Surprisingly, one clone, Hu41, had the same epitope specificity and functional in vitro activity as BSW17 and V(H) complementarity-determining regions identical with that of BSW17. Real-time PCR analysis confirmed the presence of the Hu41 V(H) sequence in the human genome. These data document the first example of the isolation of a human antibody where high sequence similarity to the original murine V(H) sequence is associated with common antigen and epitope specificity.
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Molecular Basis for Nonanaphylactogenicity of a Monoclonal Anti-IgE Antibody
Journal of immunology (Baltimore Md. : 1950), 2000Co-Authors: Michael P. Rudolf, Beda M. Stadler, Monique Vogel, Adrian W. Zuercher, Andreas Nechansky, Christine Ruf, Sylvia Miescher, Franz KricekAbstract:IgE Abs mediate allergic responses by binding to specific high affinity receptors (FcepsilonRI) on mast cells and basophils. Therefore, the IgE/FcepsilonRI interaction is a target for clinical intervention in allergic disease. An Anti-IgE mAb, termed BSW17, is nonanaphylactogenic, although recognizing IgE bound to FcepsilonRI, and interferes with binding of IgE to FcepsilonRI. Thus, BSW17 represents a candidate Ab for treatment of IgE-mediated disorders. By panning BSW17 against random peptide libraries displayed on phages, we defined mimotopes that mimic the conformational epitope recognized on human IgE. Two types of mimotopes, one within the Cepsilon3 and one within the Cepsilon4 domain, were identified, indicating that this mAb may recognize either a large conformational epitope or eventually two distinct epitopes on IgE. On the basis of alignments of the two mimotopes with the human IgE sequence, we postulate that binding of BSW17 to the Cepsilon3 region predominantly blocks binding of IgE to FcepsilonRI, leading to neutralization of IgE. Moreover, binding of BSW17 to the Cepsilon4 region may explain how BSW17 recognizes FcepsilonRI-bound IgE, and binding to this region may also interfere with degranulation of IgE sensitized cells (basophils and mast cells). As a practical application of these findings, mimotope peptides coupled to a carrier protein may be used for the development of a peptide-based anti-allergy vaccine by induction of Anti-IgE Abs similar to the current approach of using humanized nonanaphylactogenic Anti-IgE Abs as a passive vaccine.
-
Oral Anti-IgE immunization with epitope-displaying phage.
European journal of immunology, 2000Co-Authors: Adrian W. Zuercher, Monique Vogel, Michael P. Rudolf, Sylvia Miescher, Michael B. Stadler, Beda M. StadlerAbstract:An essential requirement for oral vaccines is the ability to survive the harsh environment of the stomach in an antigenically intact form. As bacteriophages are adapted to this environment we used epitope-displaying M13 bacteriophages as carriers for an experimental oral Anti-IgE vaccine. The feasibility of this approach was tested in a simulated gastric fluid using two different mimotopes as well as an anti-idiotypic Fab of the non-anaphylactogenic Monoclonal Anti-IgE antibody BSW17. All phage clones remained infective after this treatment. However, only epitopes displayed on the pVIII protein were still recognized by BSW17 whereas pIII-expressed epitopes were rapidly inactivated. Surprisingly, when used for oral immunization of mice all phage clones induced Anti-IgE antibodies. In contrast, oral immunization with the purified, pVIII protein displaying the mimotope induced anti-phage but no Anti-IgE antibodies. After feeding a single dose of mimotope-displaying bacteriophage, phage DNA could be detected in mouse feces for 10 days. Our results show that epitope-displaying bacteriophages can be used to induce an epitope-specific antibody response via the oral route.
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Mimotope and Anti–Idiotypic Vaccines to Induce an Anti–IgE Response
International archives of allergy and immunology, 1999Co-Authors: Beda M. Stadler, Sylvia Miescher, Franz Kricek, Adrian W. Zürcher, Monique VogelAbstract:We have defined epitopes on human IgE by screening different phage display random peptide libraries with a Monoclonal anti–IgE antibody termed BSW17. The selected mimotopes and epitopes within the Ce3 and Ce4 region of IgE induced antibodies that were nonanaphylactogenic and had biological activity similar to BSW17. The chemically synthesized and KLH–coupled IgE epitopes or mimotopes were used to induce an anti–IgE response in rhesus monkeys. The immunized rhesus monkeys were subsequently protected in a PCA test when sensitized with human IgE and triggered with the corresponding allergen. Furthermore, using the same Monoclonal anti–IgE antibody, we also generated an anti–idiotypic antibody that showed sequence homology with the IgE epitope in the Ce3 domain. This anti–idiotypic antibody as well as the mimotopes were then used in a mouse model to induce orally an anti–IgE immune response. For this purpose mice were fed by intragastric gavages with bacteriophages displaying the small IgE–homologous structures. Orally immunized mice produced serum anti–IgE antibodies that were inhibited by BSW17 suggesting that it may be possible to induce a systemic anti–IgE response orally.
Girolamo Pelaia - One of the best experts on this subject based on the ideXlab platform.
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Asthma: Targeted Biological Therapies
2017Co-Authors: Girolamo Pelaia, Alessandro Vatrella, Rosario MaselliAbstract:This book focuses on the fundamentals of the use of biologics in asthma, describing the rationale, principles, mechanisms of action, and indications. It offers an excellent balance between basic science and the analysis of clinical trials, updating readers with new developments that are changing the global scenario for targeted biological anti-asthma therapies, especially with regard to more severe disease. A range of therapies are considered, from the humanized Monoclonal Anti-IgE antibody omalizumab, widely approved as add-on treatment for inadequately controlled disease, through to emerging biologics for which evidence supportive of efficacy is accumulating, including anti-IL-5, anti-IL-4, and anti-IL-13 therapies. One aspect to emerge is the variability in individual response, which suggests a need for characterization of different asthma subtypes to permit the effective implementation of phenotype-targeted treatments. This book will be of interest for pulmonologists, clinical immunologists, and physicians seeking sound information on these therapies, but also for scientists and pharmacologists wishing to enhance their knowledge of the therapeutic implications of the cellular and molecular mechanisms that underlie severe, uncontrolled asthma
-
Anti-IgE therapy with omalizumab for severe asthma: current concepts and potential developments.
Current drug targets, 2015Co-Authors: Girolamo Pelaia, Luca Gallelli, Maria Teresa Busceti, Alessandro Vatrella, Rosa Terracciano, Rosario MaselliAbstract:The humanized Monoclonal Anti-IgE antibody omalizumab is currently the only biologic drug approved for asthma treatment. Omalizumab inhibits allergic responses by binding to serum immunoglobulins E (IgE), thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of down-regulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both peripheral blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Moreover, some recent studies suggest potential benefits of omalizumab also in non allergic phenotypes of severe asthma. Very interesting are also further recent reports referring to the potential inhibitory effect of omalizumab with regard to bronchial structural changes, especially occurring in severe asthma and globally defined as airway remodeling. Omalizumab is relatively well tolerated, and only very rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent asthma, inadequately controlled by high doses of standard inhaled treatments.
-
An insight into pharmacological and clinical basis of Anti-IgE for add-on therapy of severe asthma
Shortness of Breath, 2013Co-Authors: Girolamo Pelaia, Luca Gallelli, Maria Teresa Busceti, Alessandro Vatrella, Rosario MaselliAbstract:IgE antibodies are crucially involved in mediating, maintaining and amplifying the allergic cascade. The humanized Monoclonal Anti-IgE antibody omalizumab is currently the only biologic drug approved for asthma treatment. Anti-IgE inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of down-regulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both peripheral blood and induced sputum. Randomized clinical trials showed relevant clinical effects of omalizumab including improvements of respiratory symptoms and quality of life. Moreover, a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators was also observed. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for most severe patients with persistent allergic asthma, inadequately controlled by high doses of standard treatments.
-
Update on optimal use of omalizumab in management of asthma.
Journal of asthma and allergy, 2011Co-Authors: Girolamo Pelaia, Luca Gallelli, Teresa Renda, Pasquale Romeo, Maria Teresa Busceti, Rosa Daniela Grembiale, Rosario Maselli, Serafino A. Marsico, Alessandro VatrellaAbstract:Omalizumab is a humanized Monoclonal Anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.
-
Review: Omalizumab in the treatment of severe asthma: efficacy and current problems:
Therapeutic advances in respiratory disease, 2008Co-Authors: Girolamo Pelaia, Teresa Renda, Pasquale Romeo, Maria Teresa Busceti, Rosario MaselliAbstract:Omalizumab is a humanized Monoclonal Anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high-affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma, inadequately controlled by high doses of standard inhaled treatments.