| Contents | 5 |
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| Contributors | 7 |
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| 1 Introduction | 10 |
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| 1.1 Background | 10 |
| 1.2 History of Allergy | 11 |
| 1.3 History of AllergoOncology | 13 |
| 1.4 Synopsis | 17 |
| References | 17 |
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| 2 The Biology of IgE: Molecular Mechanism Restraining Potentially Dangerous High Serum IgE Titres In Vivo | 21 |
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| 2.1 Introduction | 21 |
| 2.2 Reduced Class Switch Frequency to the IgE Locus | 22 |
| 2.3 Serum IgE Has the Shortest Half-Life of All Serum Immunoglobulins | 26 |
| 2.4 CD23 Influences IgE Expression by a Negative Feedback Inhibition | 28 |
| 2.5 The Biological Function of the mIgE Antigen Receptor on IgE Synthesis In Vivo | 30 |
| 2.6 Impaired Splicing and Polyadenylation Restricts the Generation of a Mature mIgE Transcript | 32 |
| 2.7 IgE Plasmablasts Have an Intrinsic, Lower Chance to Contribute to the Long-Lived Plasma Cell Pool | 34 |
| 2.8 Conclusions | 35 |
| References | 36 |
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| 3 The Biology of IgE: The Generation ofINTtie | High-Affinity IgEAntibodies |
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| 3.1 High-Affinity Versus Low-Affinity IgE Antibodies | 45 |
| 3.2 Switching to IgE and Its Control in B Lymphocytes | 46 |
| 3.3 Sequential Switching to IgE in Mice and Humans | 48 |
| 3.4 Unique Pathway for the Generation of High-Affinity IgE Antibodies | 49 |
| 3.4.1 Summary of Findings | 49 |
| 3.4.2 Experimental Evidence | 50 |
| 3.4.2.1 IgE + Cells are Found Outside Germinal Centers in Both T/B Monoclonal Mice (T-Bmc) and Wild-Type Mice | 50 |
| 3.4.2.2 IgE Antibodies Undergo Somatic Hypermutation and Affinity Maturation | 50 |
| 3.4.2.3 IgG1 + B Cells can Generate IgE Antibodies by Sequential Switching | 51 |
| 3.4.2.4 Interleukin-21 Inhibits the Sequential Switching of IgG1 + Cells to IgE, Thus Inhibiting the High-Affinity IgE Response | 51 |
| 3.5 Conclusion | 52 |
| References | 52 |
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| 4 Epidemiological Evidence: IgE, Atopy, and Solid Tumors | 55 |
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| 4.1 Introduction | 55 |
| 4.2 Methods | 56 |
| 4.3 Results | 56 |
| 4.3.1 All Cancer | 57 |
| 4.3.2 Lung Cancer | 60 |
| 4.3.3 Pancreatic Cancer | 64 |
| 4.3.4 Tumors of the Brain and Nervous System | 68 |
| 4.3.5 Colorectal Cancer | 72 |
| 4.3.6 Reproductive Cancers | 73 |
| 4.3.7 Other Cancer Sites | 75 |
| 4.4 Discussion | 76 |
| 4.5 Conclusion | 78 |
| References | 78 |
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| 5 Epidemiological Evidence: IgE, Allergies, and Hematopoietic Malignancies | 86 |
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| 5.1 Introduction | 86 |
| 5.2 Methods of Review | 88 |
| 5.3 Leukemias | 89 |
| 5.4 Non-Hodgkin Lymphoma | 103 |
| 5.5 Hodgkin Lymphoma | 119 |
| 5.6 Plasma Cell Malignancies | 120 |
| 5.7 Conclusion Epidemiologic Findings | 129 |
| 5.8 Potential Mechanistic Interactions between Allergy/Atopy Associated with the Development of Hematopoietic Cancers | 129 |
| 5.8.1 IgE/Allergy-Mediated Enhancement of Antitumor Immunity | 130 |
| 5.8.2 Stabilization of CD23 Expression by IgE | 131 |
| 5.8.3 The Immune Regulatory Milieu Associated with Allergy may be Less Supportive for the Stimulation of B-Cell Activation and/or Resistance to Apoptosis | 133 |
| 5.8.4 Conclusion -- Potential Interactions between Allergy/Atopy Associated with the Development of Hematopoietic Cancers | 135 |
| References | 136 |
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| 6 Mast Cells in Allergy and Tumor Disease | 144 |
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| 6.1 Introduction | 144 |
| 6.2 Mast Cells in Allergy | 145 |
| 6.2.1 Allergies and Mast Cell Subsets | 145 |
| 6.2.2 Mast Cells and Dendritic Cells | 146 |
| 6.2.3 Mast Cells and T-Cells | 148 |
| 6.2.4 Mast Cells and Airway Tissue Remodeling | 149 |
| 6.3 Mast Cells in Cancer | 150 |
| 6.3.1 Introduction | 150 |
| 6.3.2 Mast Cells and Angiogenesis | 150 |
| 6.3.3 Mast Cells in Human Tumors | 152 |
| 6.3.4 Mast Cells Mediators of Tumor Growth or Rejection | 152 |
| 6.3.5 Mast Cells Regulate Adaptive Immune Responses to Tumors | 155 |
| 6.4 Conclusion | 157 |
| References | 158 |
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| 7 The IgE Antibody and Its Use in Cancer Immunotherapy | 166 |
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| 7.1 IgE and Its Relevance in Cancer Therapy | 166 |
| 7.1.1 Immunoglobulins | 166 |
| 7.1.2 The Structure of the IgE Antibody and Its Binding Properties | 168 |
| 7.1.3 The Function of IgE and Its Relevance in Cancer Therapy | 169 |
| 7.2 Reaginic Antibodies and Local Anti-Tumor Anaphylaxis | 173 |
| 7.3 Generating Tumor-Specific Monoclonal IgE | 174 |
| 7.3.1 Development of Monoclonal and Recombinant IgE | 174 |
| 7.3.2 Use of Tumor-Specific IgE for the Passive Immunotherapy of Cancer | 175 |
| 7.3.2.1 Murine IgE Specific for the Glycoprotein 36 of the Mouse Mammary Tumor Virus | 175 |
| 7.3.2.2 Rat/Human Chimeric IgE Specific for Murine CD8 | 176 |
| 7.3.2.3 Murine and Mouse/Human Chimeric IgE Specific for an Antigenic Determinant on the Surface of Colorectal Carcinoma Cells | 177 |
| 7.3.2.4 Mouse/Human Chimeric IgE Specific for Human Folate Binding Protein | 178 |
| 7.3.2.5 Engineered IgE Specific for Human HER2/ neu | 180 |
| 7.3.2.6 Chimeric IgE Targeting Human CD20 | 181 |
| 7.3.3 Induction of an Endogenous IgE Response via Mimotope Vaccination | 182 |
| 7.4 Conclusions | 183 |
| References | 185 |
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| 8 IgE Interacts with Potent Effector Cells Against Tumors: ADCC and ADCP | 191 |
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| 8.1 IgE Operates Through Powerful Fc Epsilon Receptors | 191 |
| 8.1.1 The High-Affinity IgE Receptor FcRI | 191 |
| 8.1.2 The Low-Affinity IgE Receptor (CD23) | 194 |
| 8.1.3 Galectin-3 | 195 |
| 8.2 What is Known About IgE Effector Cells in Cancer? Missing Activation Signals May Tip the Balance in Favor of Tumor Growth | 195 |
| 8.2.1 Mast Cells and Basophils | 196 |
| 8.
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