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Cancer Immunology, Immunotherapy : CII Jun 2013Immunotherapy targeting disialoganglioside GD(2) emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here,...
PURPOSE
Immunotherapy targeting disialoganglioside GD(2) emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here, we report the induction of a GD(2)-specific immune response with ganglidiomab, a new anti-idiotype antibody to anti-GD(2) antibodies of the 14.18 family.
EXPERIMENTAL DESIGN AND RESULTS
Ganglidiomab was generated following immunization of Balb/c mice with 14G2a, and splenocytes were harvested to generate hybridoma cells. Clones were screened by ELISA for mouse antibody binding to hu14.18. One positive clone was selected to purify and characterize the secreted IgG protein (κ, IgG(1)). This antibody bound to anti-GD(2) antibodies 14G2a, ch14.18/CHO, hu14.18, and to immunocytokines ch14.18-IL2 and hu14.18-IL2 as well as to NK-92 cells expressing scFv(ch14.18)-zeta receptor. Binding of these anti-GD(2) antibodies to the nominal antigen GD(2) as well as GD(2)-specific lysis of neuroblastoma cells by NK-92-scFv(ch14.18)-zeta cells was competitively inhibited by ganglidiomab, proving GD(2) surrogate function and anti-idiotype characteristics. The dissociation constants of ganglidiomab from anti-GD(2) antibodies ranged from 10.8 ± 5.01 to 53.5 ± 1.92 nM as determined by Biacore analyses. The sequences of framework and complementarity-determining regions of ganglidiomab were identified. Finally, we demonstrated induction of a GD(2)-specific humoral immune response after vaccination of mice with ganglidiomab effective in mediating GD(2)-specific killing of neuroblastoma cells.
CONCLUSION
We generated and characterized a novel anti-idiotype antibody ganglidiomab and demonstrated activity against neuroblastoma.
Topics: Amino Acid Sequence; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Base Sequence; Binding, Competitive; Cancer Vaccines; Cell Line, Tumor; Gangliosides; Humans; Kinetics; Mice; Molecular Sequence Data; Neuroblastoma; Protein Binding; Sequence Alignment
PubMed: 23591980
DOI: 10.1007/s00262-013-1413-y -
Human Vaccines & Immunotherapeutics Oct 2017Oral immunotherapy (OIT) is an emerging treatment of IgE-mediated egg allergy. In the past decade, a multitude of studies have assessed the potential for egg OIT to... (Review)
Review
Oral immunotherapy (OIT) is an emerging treatment of IgE-mediated egg allergy. In the past decade, a multitude of studies have assessed the potential for egg OIT to induce clinical desensitization. The following review will evaluate the efficacy and safety of this therapy as determined by randomized controlled, non-randomized controlled and uncontrolled trials. Recent studies using reduced allergenic egg products and anti-IgE assisted therapy to improve egg OIT safety will also be discussed. Recent advances in the mechanisms underlying food OIT suggest that certain immune parameters may be helpful in monitoring response to therapy, including egg OIT. Although, egg OIT is consistently shown to be effective with regards to clinical desensitization, fewer studies have looked at persistent tolerance or sustained unresponsiveness. Limited results of long-term follow-up trials suggest that this therapy may have disease-modifying effects. In general, the comparison of studies is complicated by major differences in study designs, OIT protocols and endpoints.
Topics: Administration, Oral; Allergens; Animals; Antibodies, Anti-Idiotypic; Clinical Trials as Topic; Desensitization, Immunologic; Egg Hypersensitivity; Eggs; Humans; Immune Tolerance; Immunoglobulin E; Immunoglobulin G; Mice; Ovalbumin
PubMed: 28696863
DOI: 10.1080/21645515.2017.1339844 -
Medical Science Monitor : International... Sep 2014Omalizumab, a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and... (Review)
Review
Omalizumab, a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cells and basophils. We found that omalizumab in patients with severe persistent asthma (SPA) was an effective therapy for asthma and the following co-morbid conditions: chronic urticaria (CU), bee venom allergy, latex allergy, atopic dermatitis, food allergy and Samter's syndrome. Information on the use of omalizumab in treatment of asthma and other allergic diseases has improved our understanding that treatment acts on many levels, including regulating levels of inflammatory proteins, including cytokines (copper-containing alpha- 2-glycoprotein, total antioxidant capacity, MDA, NO, H2O2, CXCL8, IL-10, TGF-β, GMCSF, IL-17, IL-1β), MPV, Hs-CRP, eosinophil cationic peptide, vitamin-D (25(OH)D), homocysteine (Hcy), OX-2, d- dimer, albumin, and sApo-2L. The decrease in Hcy concentrations and increase in 25(OH)D also support the existence of a vascular endothelial protection mechanism. Mediators and cells classically involved in pro-coagulant and anticoagulant pathways together play a role in SPA and CU pathophysiology and omalizumab effect. The mechanism of action of omalizumab in the treatment of asthma is believed to be multifactorial, and includes effects mediated through altered production of redox metabolites, extrinsic coagulation pathway, oxidative markers-related mi RNA, TRAIL-related mi RNA, and regulation of production of known inflammatory proteins.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Blood Coagulation; Desensitization, Immunologic; Humans; Omalizumab; Oxidative Stress; Receptors, IgE
PubMed: 25241913
DOI: 10.12659/MSM.890137 -
The Cochrane Database of Systematic... Mar 2018Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Early Termination of Clinical Trials; Humans; Itraconazole; Omalizumab; Randomized Controlled Trials as Topic
PubMed: 29551015
DOI: 10.1002/14651858.CD010288.pub4 -
Autoimmunity Jun 2012Circulating autoantibodies to beta cell antigens are present in the majority of patients with Type 1 diabetes. These autoantibodies can be detected before and at time of... (Review)
Review
Circulating autoantibodies to beta cell antigens are present in the majority of patients with Type 1 diabetes. These autoantibodies can be detected before and at time of clinical diagnosis of disease. Although the role of autoantibodies in the pathogenesis of the disease is debated, their presence indicates a dysregulation of the humoral immune response. Mechanisms regulating autoantibodies in Type 1 diabetes are not well understood. In contrast, in other autoimmune diseases there is acceptance that autoantibodies are regulated not only by antigen but also by other antibodies that bind to the antigen-binding site of these autoantibodies (anti-idiotypic antibodies). The proposed purpose of this network is to maintain an equilibrium between autoantibodies and their anti-idiotypic antibodies, preventing autoimmunity, while allowing a robust response to exogenous antigen. Anti-idiotypic antibodies regulate both autoantibody binding and their levels by a) neutralizing autoantibodies, and b) inhibiting the secretion of autoantibodies. Because it has been proposed that the B lymphocytes that produce autoantibodies function as autoantigen presenting cells, inhibiting their binding to autoantigen by anti-idiotypic antibodies may prevent development of autoimmune disease. This hypothesis is supported by the presence of anti-idiotypic antibodies in healthy individuals and in patients in remission from autoimmune diseases, and by the lack of anti-idiotypic antibodies during active disease. We recently reported the presence of autoantibodies to glutamate decarboxylase in the majority of healthy individuals, where their binding to autoantigen is prevented by anti-idiotypic antibodies. These anti-idiotypic antibodies are absent at clinical diagnosis of Type 1 diabetes, revealing the presence of autoantibodies. Type 1 diabetes (T1D) is an autoimmune disease characterized by the dysfunction and destruction of insulin-producing beta cells by autoreactive T cells. Although much progress has been made towards understanding the respective roles of effector and regulatory T cells in this beta cell destruction, the development of autoantibodies to beta cell proteins is widely considered simply a by-product of the autoimmune destruction of the beta cells, rather than having an active role in the pathogenesis. This view is starting to change based on increasing recognition that autoantibodies can have defined roles in other autoimmune diseases, and the emergence of new data on their role in T1D. This exploration of the role of autoantibodies in autoimmune disease has been spurred, in part, by increasing recognition that development of autoimmune diseases is influenced by regulatory antibodies (anti-idiotypic antibodies) directed against the unique binding site of autoantibodies. This review provides an overview of the development and function of these anti-idiotypic antibodies, and present evidence supporting their role in the development of autoimmune diseases. Finally, we conclude this review with a model of the events that may cause loss of anti-idiotypic antibodies and the implications for the development of T1D.
Topics: Antibodies, Anti-Idiotypic; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; Diabetes Mellitus, Type 1; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; T-Lymphocytes
PubMed: 22288464
DOI: 10.3109/08916934.2012.659299 -
Proceedings of the National Academy of... Jan 1996There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with... (Review)
Review
There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other protein-protein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogen-bond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding. For the most studied antigen, lysozyme, the epitopes for four antibodies occupy approximately 45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Viral; Bacterial Proteins; Binding Sites, Antibody; Chickens; Epitope Mapping; Epitopes; Immunoglobulin Fab Fragments; Mice; Models, Molecular; Muramidase; Neuraminidase; Orthomyxoviridae Infections; Phosphoenolpyruvate Sugar Phosphotransferase System; Protein Binding; Protein Conformation; Structure-Activity Relationship; X-Ray Diffraction
PubMed: 8552677
DOI: 10.1073/pnas.93.1.7 -
Actas Dermo-sifiliograficas 2014Omalizumab is a monoclonal anti-immunoglobulin E antibody currently only approved for use in severe, refractory asthma. In recent years, many authors have reported... (Review)
Review
Omalizumab is a monoclonal anti-immunoglobulin E antibody currently only approved for use in severe, refractory asthma. In recent years, many authors have reported satisfactory results with omalizumab in patients with difficult-to-treat chronic urticaria. As a result, clinical trials were undertaken to broaden the indication of omalizumab to include chronic urticaria, and the drug was recently cited as a third-line treatment after selective antihistamines at high doses in a consensus document on the treatment of chronic urticaria. In this article our aim is to provide a comprehensive update on the use of omalizumab in the treatment of chronic urticaria. The structure of this biologic agent and its possible mechanisms of actions in this setting will be presented. Treatment strategies and the different dosage regimens used in the series of cases published to date will also be reviewed. Finally, we will discuss the adverse effects that may arise with treatment and the recommended strategies for minimizing the most feared effect, anaphylaxis. Based on the experience of many researchers, omalizumab is emerging as a novel treatment for certain types of spontaneous refractory chronic urticaria and has shown promising results in this setting. The drug has a good safety profile and the main limitation is its high cost.
Topics: Anti-Allergic Agents; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Asthma; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Immunity, Cellular; Immunoglobulin E; Multicenter Studies as Topic; Omalizumab; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Receptors, IgE; Urticaria
PubMed: 23938072
DOI: 10.1016/j.ad.2013.06.002 -
MSphere Oct 2018The immunoprophylactic potential of anti-idiotype (anti-id) foot-and-mouth disease (FMD) antigen (Ag) was evaluated in the calves. The idiotype antibodies (Ab1) were...
The immunoprophylactic potential of anti-idiotype (anti-id) foot-and-mouth disease (FMD) antigen (Ag) was evaluated in the calves. The idiotype antibodies (Ab1) were produced in experimental goats by injecting inactivated FMD virus. The Fab (fragment antigen binding) of Ab1 was injected into the layer birds to raise anti-id antibodies (Ab2). The Ab2 was purified from egg yolks. The Fab component of Ab2 was emulsified in Montanide (1:1) and used as a surrogate of FMD virus. The immune response to Montanide adjuvanted monovalent and trivalent anti-id FMD virus antigen was determined in mice. The comparative immune potentiation potentials of Montanide adjuvanted trivalent anti-id FMD virus antigen and trivalent FMD vaccine were determined in mice and calves. Montanide adjuvanted monovalent anti-id FMD virus antigens produced mean Ab titers of 78.80%, 81.30%, and 81.20% for serotypes A, Asia 1, and O, respectively, at 45 days postimmunization (p.i.) in mice. Montanide adjuvanted trivalent anti-id FMD Ag in mice produced the highest Ab titer, 81.60%, at day 45 compared to the 77.50% titer measured for Montanide adjuvanted FMD vaccine at day 45 p.i. A slow decrease of 1% to 2% was recorded for the Ab titer of Montanide adjuvanted trivalent anti-id FMD virus antigen in mice at day 60. In calves, the titer corresponding to the immune response seen with Montanide adjuvanted trivalent anti-id FMD virus antigen (80%) was persistent whereas the titer of Montanide adjuvanted FMD vaccine decreased to 74% at day 60 p.i. Anti-id FMD virus antigen induced a strong and persistent immunogenic response in terms of Ab titer compared to the inactivated virus vaccine. Anti-id FMD virus antigen may serve as a surrogate of FMD virus vaccine. Foot-and-mouth disease (FMD) is a contagious viral disease of animals. Multiple serotypes and antigenic variation in the viral genome are probably the factors that reduce control of the disease. Currently, the vaccines employed against FMD use killed virus. The inactivation or killing of the virus makes it less immunogenic and reduces its immunoprophylactic potential. To cope with this situation, the present study was designed, anti-idiotype FMD virus antigen was prepared, and the immunogenic potential of the antigen was compared to that of commercial killed-virus vaccines. The overall results showed that a persistent and strong immune response occurred with anti-idiotype FMD virus antigen. Thus, anti-idiotype FMD virus antigen may serve as a potential surrogate of FMD virus vaccines.
Topics: Adjuvants, Immunologic; Animals; Antibodies, Anti-Idiotypic; Antibodies, Viral; Antigens, Viral; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Goats; Immunity, Cellular; Immunity, Humoral; Mice; Mice, Mutant Strains; Viral Vaccines
PubMed: 30333183
DOI: 10.1128/mSphere.00522-18 -
Journal of Korean Medical Science May 2012The elastin metabolism in systemic sclerosis (SSc) has been known to be abnormal. The authors investigated relationship between the clinical manifestations of systemic...
The elastin metabolism in systemic sclerosis (SSc) has been known to be abnormal. The authors investigated relationship between the clinical manifestations of systemic sclerosis (SSc) and serum levels of soluble elastin-derived peptide (S-EDP) and anti-elastin antibodies. Serum samples were obtained from 79 patients with SSc and 79 age- and sex-matched healthy controls. Concentrations of serum S-EDP and anti-elastin antibodies were measured by ELISA. The serum concentrations of S-EDP in SSc patients were significantly higher than in healthy controls (median, 144.44 ng/mL vs 79.59 ng/mL, P < 0.001). Serum EDP concentrations were found to be correlated with disease duration in SSc (P = 0.002) and particularly in diffuse cutaneous SSc (P = 0.005). Levels of anti-elastin antibodies were found to be more elevated in SSc patients than in healthy controls (median, 0.222 U vs 0.191 U, P = 0.049), more increased in diffuse cutaneous SSc than limited cutaneous SSc (median, 0.368 U vs 0.204 U, P = 0.031). In addition, levels of anti-elastin antibodies were also found to be negatively associated with presence of anti-centromere antibody (P = 0.023). The S-EDP levels were not found to be correlated with levels of anti-elastin antibodies. The increased S-EDP and anti-elastin antibody levels and association with clinical and laboratory characteristics may reflect the abnormal metabolism in SSc.
Topics: Adult; Antibodies, Anti-Idiotypic; Centromere; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Peptides; Scleroderma, Systemic
PubMed: 22563211
DOI: 10.3346/jkms.2012.27.5.484 -
Asian Pacific Journal of Allergy and... Sep 2014Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a... (Review)
Review
Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a significant focus for treating food allergies, and oral immunotherapy (OIT) appears to be particularly effective in inducing desensitization. The majority of patients who receive OIT show increased threshold doses of their food allergen. The efficacy of OIT is different among food antigen, and milk OIT is relatively difficult to achieve tolerance. OIT may induce mild to moderate symptoms during the therapy, widespread acceptance of OIT for long-term therapy is unclear. Recently, novel immunotherapies for food allergies, such as sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) and using an anti-IgE monoclonal antibody (omalizumab), have been assessed. In addition, a combination of OIT with omalizumab, which was found to increase the threshold doses of the offending foods without producing adverse reactions, may be effective and useful in the treatment of food allergies. These treatments have been used only in research settings; further studies in large numbers of patients are needed to demonstrate their long-term safety and benefits in clinical practice.
Topics: Animals; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antigens; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immune Tolerance; Omalizumab
PubMed: 25268336
DOI: No ID Found