醫(yī)學免疫學課件：抗IgE抗體治療I型超敏反應疾病的進展

1、The Development of Anti-IgE Antibody in Treating Type I Hypersensitivity點擊添加文本點擊添加文本點擊添加文本點擊添加文本Anti-IgE antibodyApplicationIntroductionProspect點擊添加文本點擊添加文本點擊添加文本點擊添加文本AllergenIgE and Type I HypersensitivityMechanismSymptomJaneways immunobiology 8th edition, fig 14.3Fig 1. Sensitization to an inhale

2、d allergenIntroductionJaneways immunobiology 8th edition, fig 14.2Fig 2. Common allergens and IgE-mediated allergic reactionsIntroductionJaneways immunobiology 8th edition, fig 14.4Fig 3. Antigen binding to lgE on mast cells or basophils leads to amplification of IgE productionIntroductionFig 4. Mas

3、t-cell activation has different effects on different tissuesJaneways immunobiology 8th edition, fig 14.10IntroductionJaneways immunobiology 8th edition, fig 14.15Fig 5. The acute response in allergic asthma leads to Th2-mediated chronic inflammation of the airways.Introduction點擊添加文本點擊添加文本點擊添加文本點擊添加文

4、本StructureDevelopmentFunctionFightAgainstIgEAntiIgEAntibodyDevelopment of OmalizumabAnti-IgE?!CDR graftingAnti-IgE antibodyAnti-IgE antibodyAnti-IgE antibodyComplementarity determining RegionFrame RegionConstant RegionOmalizumab A Anti-IgE antibodyFig 6. Structure of Omalizumab Fab fragmentProtein M

5、MDB ID: 128121 PD ID:4X7T Anti-IgE antibodyAnti-IgE antibodyAnti-IgE antibodyComplementarity determining RegionFrame RegionConstant RegionFig 7. Structure of IgE Fc domain in complex with a neutralizing antibody Protein MMDB ID: 133123 PD ID:5ANM Fig 8. Structure definition Anti-IgE-IgE interactionE

6、 Suzanne Cohen, mABs,A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma, May 2014Anti-IgE antibody點擊添加文本點擊添加文本點擊添加文本點擊添加文本Application of Anti-IgE AntibodyAnti-IgE antibodyAni-IgE antibodyApplicationApproved in Clinical Use Severe Allergic Asthma(2004)Improving symptom

7、controlReducing frequency of exacerbationsReducing dose of inhaled corticosteroidsReducing hospitalizations and emergency room visiting times Chronic Intrinsic Urticaria, CIU(2014)Anti-IgE antibodyAni-IgE antibodyApplicationCombine Treatment with SITProsFewer systemic adverse reactionsLower intensit

8、y of symptomsHigher dose of immunotherapyImproved quality of lifeCons High priceSpecificImmunotherapyAllergicReactionApplicationOther Allergy Proved in Clinical TrailsAllergic Rhinitis/ RhinosinusitisNasal polyposisLatex AllergyAtopic DermatitisFood AllergyIntroductionApplicationNON-Allergic Dieases

9、Non-allergic (Intrinsic) AsthmaCIU OutlookLommatzsch, M., et al., Against all odds: anti-IgE for intrinsic asthma? Thorax, 2013. 69(1): p. 94-96.Fig 2. Possible mechanisms of anti-IgE treatment in intrinsic asthmaFig 2. Diagram showing the hypothetical impact of Staphylococcus aureus (SA) superantig

10、ens on the development of IgE-related severe asthma.Bachert, C. and N. Zhang, Chronic rhinosinusitis and asthma: novel understanding of the role of IgE above atopy. Journal of Internal Medicine, 2012. 272(2): p. 133-143OutlookIntroductionApplicationSide EffectsCommon side effects same as other commo

11、n drugsSpecial side effect anticoagulation cardiovascular safety problemsIntroductionApplicationCost-Effectiveness Ratio40,000 /Quality-Adjusted Life-Year (QALY)Higher Asthma Control Test (ACT) score Higher Asthma Control Questionnaire (ACQ)Regularly treatment saving other medical costApplicationLow

12、 AffinityHigh PriceSetbackAnti-IgE antibodyComplementarity determining RegionFrame RegionConstant RegionOutlookMy ThoughtClinical MedicinePreclinical MedicineMy ThoughtClinical MedicinePreclinical MedicineReference1.Incorvaia, C., et al., Omalizumab, an anti-immunoglobulin e antibody: state of the a

13、rt. DRUG DES DEV THER. 2014(8): p. 197-207.2.Yalcin, A.D., An Overview of the Effects of anti-IgE Therapies. Medical Science Monitor, 2014. 20: p. 1691-1699.3.Bousquet, J., et al., The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in

14、patients with severe persistent asthma. Allergy, 2005. 60(3): p. 302-8.4.Roth, M., et al., Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab. PLOS ONE, 2015. 10(9): p. e0136549.5.Yalcin, A.D., et al., Clinical course and side effects of

15、 anti-IgE monoclonal antibody in patients with severe persistent asthma. Clin Lab, 2013. 59(1-2): p. 71-7.6. Cohen, E.S., et al., A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma. MAbs, 2014. 6(3): p. 756-64.7.van Nooten, F., et al., Cost-effectiveness of omalizumab

16、for uncontrolled allergic asthma in the Netherlands. J Med Econ, 2013. 16(3): p. 342-8.8.Bachert, C. and N. Zhang, Chronic rhinosinusitis and asthma: novel understanding of the role of IgE above atopy. Journal of Internal Medicine, 2012. 272(2): p. 133-143.9.Lowe, P.J. and D. Renard, Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE. British Journal of Clinical Pharmaco