Lustgarten / Cui / Li Targeted Cancer Immune Therapy

1. Auflage 2009
ISBN: 978-1-4419-0170-5
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 343 Seiten

Stimulation of the immune system's ability to control and destroy tumors cont- ues to be the goal of cancer immune therapy; but the scope has rapidly expanded; approaches are constantly updated; new molecules are continually introduced; and immune mechanisms are becoming better understood. This book has no intention of covering every aspect of immune therapy but rather focuses on the novelty of cancer immune therapy in an attempt to give readers an opportunity to absorb the new aspects of immune therapy from a single source. In this regard, three areas were selected: cytokine immune therapy, cell-based immune therapy, and targeted immune therapy. In each of these three sections, only the novel aspects of immune therapy were described instead of attempting to cover any historical achievement. In the first section, Cytokine Immune Therapy, the IL12 family, IL18, IL21, IL24, IL28, and IL29 were emphasized in regard to the an- tumor function and application in treating tumors. Most of these selected cyt- ines were discovered in last 10 years. In the second section, Cell-based Immune Therapy, the focus was engineering potent immune regulatory or effector cells such as dendritic cells, T cells, and stem cells. Cell engineering design is primarily based on the increased understanding of the interaction of tumor antigen-presenting cells, antigen- specific effector cells, and the tumor microenvironment.

Autoren/Hrsg.

Lustgarten, Joseph

Cui, Yan

Li, Shulin

Inhaltsverzeichnis

1;Preface;5
2;Contents;7
3;Contributors;9
4;Part I Cytokine Immune Therapy;12
5;Role of IL12 Family in Regulation of Antitumor Immune Response;13
5.1;Introduction;13
5.2;Aberrant Expression of IL12 Family Member Receptors and Subunits;14
5.3;Role of IL23 in Tumor;17
5.4;Role of IL27 in Tumor;19
5.5;Role of IL12 Family in Treg Cells;22
5.6;II35;24
5.7;References;25
6;IL-18 in Regulation of Antitumor Immune Response and Clinical Application;29
6.1;Introduction;29
6.1.1;IL-18 Receptor;30
6.1.2;IL-18 Receptor Signal Transduction;31
6.1.3;IL-18 Regulation by IL-18-Binding Protein;32
6.2;IL-18 in Regulation of Antitumor Immune Response;34
6.2.1;IL-18 in IFNg and Th1 Response Induction;34
6.2.2;IL-18 in NK Cell Activation;35
6.2.3;IL-18 in Cytotoxic T Cell Activation;36
6.3;IL-18 as a Precancerous Factor;36
6.3.1;IL-18 in Tumor Growth and Immune Evasion;37
6.3.2;IL-18 in Tumor Angiogenesis;37
6.3.3;IL-18 in Tumor Metastasis;38
6.4;IL-18 as a Cancer Prognostic Marker;40
6.5;IL-18 in Cancer Therapy;42
6.6;Summary;46
6.7;References;48
7;Interleukin-21 and Cancer Therapy;52
7.1;Introduction;52
7.2;Preclinical Data;54
7.2.1;Effects of IL-21 on T Cells;54
7.2.1.1;CD4+ T Cells;54
7.2.1.2;CD8+ T Cells;55
7.2.1.3;T Regulatory Cells;56
7.2.2;Effects of IL-21 on NK Cells and NKT Cells;56
7.2.3;Effects of IL-21 on B Cells;57
7.2.4;Animal Tumor Studies;57
7.2.4.1;IL-21 Monotherapy;57
7.2.4.2;IL-21 Combination Therapies;59
7.3;Human Clinical Trials;59
7.3.1;IL-21 Monotherapy;59
7.3.2;IL-21 Combination Therapies;60
7.4;Future Strategies;63
7.4.1;Chemotherapy;63
7.4.2;Vaccines and Adoptive Cell Therapy;63
7.4.3;Immune Modulation Such as Anti-CTLA-4 or Treg Depletion;64
7.5;Summary;64
7.6;References;65
8;IL-24 in Regulation of Antitumor Immune Response and in Signaling;69
8.1;Introduction;69
8.2;MDA-7 as a Cytokine;71
8.3;MDA-7/IL-24 Induced Apoptosis in Cancer Cells;73
8.4;MDA-7/IL-24 Inhibits Angiogenesis in Cancer Cells;75
8.5;MDA-7/IL-24 in Tumor Metastases and Invasion;76
8.6;Clinical Evaluation of MDA-7/IL-24;77
8.7;Summary;79
8.8;References;79
9;IL-28 and IL-29 in Regulation of Antitumor Immune Response and Induction of Tumor Regression;83
9.1;Introduction;83
9.1.1;Type III IFN-Encoding Genes;85
9.2;Sources and Regulation of Type III IFNs Production;85
9.3;Type III Interferon Receptor Subunit IL-28 Receptor;87
9.4;Type III IFN-Induced Signal Transduction;89
9.5;Antitumor Effects of Type III IFN;90
9.6;Conclusions and Perspectives;99
9.7;References;100
10;Passive and Active Tumor Homing Cytokine Therapy;104
10.1;Introduction;104
10.2;Passive Targeting with Poly-Ethylene Glycol;106
10.3;Active Ligand Targeting with Tumor-Homing Peptides;109
10.4;Active Targeting with Tumor-Targeted Antibodies;114
10.5;Summary;117
10.6;References;118
11;Part II Cell-based Immune Therapy;121
12;New Strategies to Improve Tumor Cell Vaccine Therapy;122
12.1;Introduction;122
12.2;Increasing the Immunogenicity of Tumor Cell Vaccines;123
12.2.1;The Immunogenicity of Tumor Cell Vaccines;123
12.2.2;Transduction of Costimulatory Molecules in the Tumor Cell Vaccine;124
12.2.3;Transduction of GM-CSF in Tumor Cell Vaccines;125
12.2.4;Using Allogeneic Tumor Cell Vaccine to Improve the Immunogenicity;126
12.2.5;Genetic Approaches to Increase the Immunogenicity of Tumor Cell Vaccines Using Viral Vectors;127
12.3;Improving the Immunological Response of Tumor Cell Vaccines;129
12.3.1;Improving the Cross-Priming of CD8+ T Cells;129
12.3.2;Blockade of Coinhibitory Signals in Immunization;130
12.3.3;Enhancing the Recall Responses of Tumor-Reactive Memory T Cells;132
12.4;Summary;133
12.5;References;133
13;Modification of Dendritic Cells to Enhance Cancer Vaccine Potency;137
13.1;Introduction;137
13.1.1;Immunotherapy has Emerged as an Alternative Treatment for Cancer;137
13.1.2;Importance of DCs for Cancer Immunotherapy;138
13.1.3;Modification of the Properties of DCs;138
13.2;Strategies to Enhance Vaccine Potency by Modifying the Properties of Dendritic Cells In Vivo;142
13.2.1;Increasing the Number of Antigen-Expressing DCs;142
13.2.2;Enhancing Antigen Expression, Processing, and Presentation in DCs;143
13.2.3;Promoting DC Activation and Function;145
13.2.4;Enhancing DC and T Cell Interaction;146
13.3;Strategies to Enhance Vaccine Potency by Modifying the Properties of Dendritic Cells Ex Vivo;148
13.3.1;Increasing the Number of Antigen-Expressing DCs;149
13.3.2;Enhancing Antigen Expression, Processing, and Presentation in DCs;151
13.3.3;Strategies to Promote DC Activation and Function;151
13.3.4;Enhancing DC and T Cell Interaction;152
13.3.5;Clinical Trials with Ex Vivo Generated DC-Based Vaccines;153
13.4;Summary;154
13.5;References;155
14;Dendritic Cell Vaccines for Immunotherapy of Cancer: Challenges in Clinical Trials;162
14.1;Introduction;162
14.1.1;Preclinical Experience of DC-Based Cancer Vaccines and Therapies;163
14.1.2;Shared Antigens;165
14.1.3;Tumor-Associated Antigen Classification;166
14.1.4;Peptide-Based Vaccines;167
14.1.5;Protein-Loaded and Antigen-Engineered DCS;167
14.1.6;First Generation Clinical Trials Utilizing DC-Based Cancer Therapy;168
14.1.7;Limited Clinical Results for DC-Based Vaccines;170
14.1.8;Next Generation Clinical Trials;172
14.1.9;Sources of Tumor Antigen;172
14.2;Summary;173
14.3;References;173
15;A “Toll Bridge” for Tumor-Specific T Cells;176
15.1;Introduction;176
15.1.1;T Cell-Based Tumor Immunotherapy;177
15.1.2;T Cell Activation and Differentiation;179
15.1.3;Effects of Toll-Like Receptor Engagement on T cells;179
15.1.3.1;Regulation of TLR Expression on T Cell Subsets;179
15.1.3.2;Potential Impact on Clonal Expansion;181
15.1.3.3;CTL Effector Function;182
15.1.3.4;Memory T Cell Development, Persistence, and Migration;183
15.1.3.5;Modulating Regulatory CD4+ T Cell Function;184
15.1.3.6;Does TLR Engagement on T Cells Occur In Vivo?;185
15.1.3.7;When TCR and TLR Signals Collide;187
15.1.4;Synergistic Effects of TLR Stimulation with Anticancer Chemotherapy or Radiation Therapy;187
15.1.5;Exploiting TLR Signals Within T Cells to EnhanceAntitumor Immunity;188
15.2;Summary;189
15.3;References;189
16;Engineering Adult Stem Cells for Cancer Immunotherapy;193
16.1;Introduction;193
16.2;Stem Cell Biology;194
16.2.1;ESC;195
16.2.2;HSC;195
16.2.3;MSC;196
16.2.4;Umbilical Cord Blood Stem Cells;196
16.2.5;Adult Tissue-Resident Stem Cells;196
16.3;HSC for Tumor Immune Therapy-Arming Stem Cells;197
16.3.1;HSCT for Hematological Malignancy and Solid Tumors: GVL and GVT;197
16.3.2;DC-Targeted Immune Therapy from Engineered HSC;198
16.3.3;T Cell-Targeted Immune Therapy Using Engineered HSC;199
16.4;MSC for Immune Therapy;200
16.4.1;Immunotherapy Through Tumor Attraction and Cytokine Production;201
16.4.2;MSC in the Context of HSCT;202
16.5;Requirement and Consideration for Stem Cell Engineering for Therapeutic Use;203
16.6;Summary;204
16.7;References;205
17;Animal Models for Evaluating Immune Responses of Human Effector Cells In Vivo;209
17.1;Introduction;210
17.2;First Models for Human Immune Cell Engraftment;211
17.3;Improvement in Animal Models for Human Leukocyte and Stem Cell Engraftment;212
17.3.1;Overall Suppression of NK Activity;212
17.3.2;b2mnull Mice;213
17.3.3;The IL2Rg..c-/- Mouse;214
17.3.4;The NOD/SCID/IL2Rg.c-/- Mouse;214
17.3.5;Other Immunodeficient Mouse Models;215
17.4;Stem Cell Sources and Route of Stem Cell Delivery;215
17.4.1;NOD/SCID/gcnull Mice Support Human Cell Engraftment from a Variety of Stem Cell Sources;216
17.4.2;Routes of Human Stem Cell Injection Have Moderate Effects on Their Engraftment in NOD/SCID/gcnull Mice;216
17.5;Multilineage Differentiation of Human Stem Cells in NOD/SCID/gcnull Mice to Functional Effectors;217
17.6;Use of Humanized Mice as an Experimental Model to Evaluate Human Immune Responses;219
17.6.1;Functional Immune Response of Differentiated Human Immune Cells Against EBV in the Humanized Mice;220
17.6.2;Functional Human Immune Responses Against HIV in the Humanized Animal Models;221
17.7;Future Directions;222
17.8;Summary;223
17.9;References;223
18;Part III Targeted Immune Therapy;226
19;CD40 Stimulation and Antitumor Effects;227
19.1;Introduction;227
19.2;CD40 and Antitumor Responses: Bridging the Gap Between Innate and Adaptive Immunity;228
19.3;Anti-CD40 and Interleukin-2: Coordination of Innate and Adaptive Immunity;230
19.4;CD40 Signaling on Tumor Cells: Activation-Induced Cell Death and Cytokine Production;231
19.5;CD40 Stimulation and Vascular Effects: Another Antitumor Pathway;233
19.6;Further Considerations: Properties of Agonist CD40 Antibodies and Potential Toxicities;234
19.7;Summary;236
19.8;References;236
20;Immunocytokines: A Novel Approach to Cancer Immune Therapy;240
20.1;Introduction;240
20.2;Immunocytokine Structures;241
20.3;Targeting Concepts;242
20.4;Immunocytokines Containing Modified IL-2;243
20.5;Effector Cell Mechanisms;244
20.6;Evidence for Antitumor Activity in Mouse Tumor Models;246
20.7;Early Clinical Studies of Immunocytokines;247
20.8;Future Directions;250
20.9;References;253
21;Immune Escape: Role of Indoleamine 2,3-Dioxygenase in Tumor Tolerance;256
21.1;Introduction to Cancer Immunoediting: Immune Surveillance, Equilibrium, and Escape;256
21.2;Indoleamine 2,3-Dioxygenase;261
21.3;IDO in Human Cancer and Immune Disorders;262
21.4;IDO2: A Second Tryptophan Catabolic Enzyme;265
21.5;Cellular Pathways of Tryptophan Catabolism Signaling Regulating T Cell Immunity;266
21.6;Dendritic Cells and Immune Tolerance Mediated by IDO;269
21.7;IDO as a Target for Therapeutic Intervention;274
21.8;Concluding Comments;276
21.9;References;277
22;Adoptive Transfer of T-Bodies: Toward an Effective Cancer Immunotherapy;283
22.1;Introduction;284
22.2;Use of Engineered T Cells for Cancer Immunotherapy;286
22.2.1;Optimization of the Chimeric Receptor Function;286
22.2.1.1;Optimal Recognition of Tumor Antigens;287
22.2.1.2;Combining Costimulatory and Stimulatory Signals;287
22.2.1.3;Signaling Domains;289
22.2.2;Increasing the Survival and Efficacy of the T-Bodies;290
22.2.2.1;Elimination of Immunosuppressive Cells;290
22.2.2.2;Minimizing the Competition for Homeostatic Cytokines;291
22.2.2.3;Improved Availability of APC and Their Function;291
22.2.3;Optimizing the Safety of the Transferred T-Bodies;292
22.3;Transduction of Human T Cells: Generation of T-Bodies Toward Clinical Applications;292
22.3.1;T Cell Differentiation State;292
22.3.2;Expanding the Modified T Cell Populations;293
22.4;Summary and Conclusions;294
22.5;References;294
23;Targeting Toll-Like Receptor for the Induction of Immune and Antitumor Responses;298
23.1;Introduction;298
23.2;TLR4;299
23.3;TLR3;302
23.4;TLR5;304
23.5;TLR7;306
23.6;TLR9;308
23.7;Summary;310
23.8;References;311
24;Manipulating TNF Receptors to Enhance Tumor Immunity for the Treatment of Cancer;316
24.1;Introduction;316
24.2;Structural and Signaling Features;317
24.3;Expression;318
24.4;Antitumor Responses;319
24.5;CD27;321
24.6;GITR;322
24.7;CD134 (OX40);323
24.8;CD137 (4-1BB);326
24.9;Clinical Application;327
24.10;Summary;330
24.11;References;330
25;Index;334