Cancer and IgE (eBook)

Contents 5
Contributors 7
1 Introduction 10
1.1 Background 10
1.2 History of Allergy 11
1.3 History of AllergoOncology 13
1.4 Synopsis 17
References 17
2 The Biology of IgE: Molecular Mechanism Restraining Potentially Dangerous High Serum IgE Titres In Vivo 21
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
3 The Biology of IgE: The Generation ofINTtie High-Affinity IgEAntibodies
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
4 Epidemiological Evidence: IgE, Atopy, and Solid Tumors 55
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
5 Epidemiological Evidence: IgE, Allergies, and Hematopoietic Malignancies 86
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
6 Mast Cells in Allergy and Tumor Disease 144
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
7 The IgE Antibody and Its Use in Cancer Immunotherapy 166
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
8 IgE Interacts with Potent Effector Cells Against Tumors: ADCC and ADCP 191
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
8.2.2 Monocytes/Macrophages 197
8.2.3 Eosinophils 198
8.2.4 Natural Killer Cells 199
8.2.5 Antigen-Presenting Cells 199
8.3 Evidence for IgE and Effector Cell-Mediated Anti-Tumoral Responses 200
8.3.1 Evidence for PBMC and Monocyte Activities in IgE-Mediated Anti-Tumoral Responses 200
8.3.2 Chimeric Ovarian Carcinoma Antigen-Specific MOv18 IgE -- Efficacy and Effector Cells 201
8.3.3 Lessons on the MOv18 IgE-Mediated Tumor Killing Mechanisms -- ADCC 203
8.3.4 MOv18 IgE-Mediated Tumor Killing Mechanisms -- ADCP 205
8.3.5 In Vitro Evidence from a Trastuzumab IgE Study 208
8.3.6 Experimental Evidence Supporting Stimulation of Mast Cells, Basophils and Eosinophils by IgE 209
8.3.7 IgEs Against Pancreatic Cancer -- A Case for Patient-Derived IgE Antibodies and Their Effector Functions 211
8.4 Conclusion 211
References 212
9 IgE as Adjuvant in Tumor Vaccination 220
9.1 Introduction 220
9.2 Mouse IgE is Responsible for Decreased Tumor Growth and Improved Mice Survival 221
9.2.1 Cell Types Involved in IgE-Induced Tumor Protection 222
9.2.2 IgE is an Adjuvant in Tumor Vaccination 223
9.2.3 Vaccinia Virus and MVA as Cell Killing Agents Coupled to IgE Loading 225
9.2.4 MVA as a Resource for Human Therapy and Recombinant Protein Expression 226
9.2.5 Use of Transgenic Mice as Tools to Explore IgE Receptor Involvement and Implement Human IgE 227
9.2.6 FcRI is Crucial for IgE Adjuvanticity in Tumor Vaccination 228
9.2.7 Implementation of Mouse Membrane-Bound IgE by Recombinant MVA 229
9.2.8 FcRI Humanized Mice Allow the Use of Human IgE in Tumor Vaccination 230
9.3 Conclusion 231
References 232
10 The Targets of IgE: Allergen-Associated andTumor-Associated Molecular Patterns 235
10.1 Background: IgE and the Anaphylactic Reaction 235
10.2 Crosslinking of Antigens A Biological Tool for Immunoregulation 236
10.3 Crosslinking Indispensable for IgE Synthesis and Pathophysiology 239
10.4 AAMPs: Allergen-Associated Molecular Patterns 242
10.5 TAMPs: Tumor-Associated Molecular Patterns 246
10.6 Conclusion 248
References 248
11 The Role of Th2-Mediated Anti-Tumor Immunityin Tumor Surveillance and Clearance 259
11.1 Introduction 259
11.2 CD4 + T cells The Th1 and Th2 Paradigm in Tumor Biology 260
11.3 Key Cellular and Chemical Mediators Involved in Th2-Mediated Tumor Immunity 261
11.3.1 Th2 Cytokines 261
11.3.2 Eosinophils and Eosinophil-Derived Mediators 266
11.3.3 Alternatively Activated Macrophages 268
11.3.4 B Cells, IgG and IgE 269
11.3.5 Mast Cells and Mast-Cell Mediators 270
11.3.6 Tc2 Cells 271
11.4 Conclusion 272
References 272
Subject Index 280