Cancer immune therapy: current and future strategies
Saved in:
| Format: | Book |
|---|---|
| Language: | English |
| Published: |
Weinheim
Wiley-VCH
2002
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXVI, 408 S. Ill., graph. Darst. |
| ISBN: | 352730441X |
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| 245 | 1 | 0 | |a Cancer immune therapy |b current and future strategies |c ed. by G. Stuhler ... |
| 264 | 1 | |a Weinheim |b Wiley-VCH |c 2002 | |
| 300 | |a XXVI, 408 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
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| 650 | 4 | |a Cancer - Immunothérapie | |
| 650 | 4 | |a Tumeurs - Immunologie | |
| 650 | 4 | |a Cancer |x Immunotherapy | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Neoplasms |x therapy | |
| 650 | 4 | |a Tumors |x Immunological aspects | |
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| adam_text | I VII
Contents
List of Contributors XVII
Color Plates XIX
Part 1 Tumor Antigenicity
1 Search for Universal Tumor Associated T Cell Epitopes 3
Robert H. Vonderheide and Joachim L. Schultze
1.1 Introduction 3
1.2 T Cell Epitopes as the Basis for Anti Cancer Therapy 4
1.3 Identification of Tumor Associated Antigens 5
1.4 Search for Universal Tumor Antigens 6
1.5 Epitope Deduction 6
1.6 Identification of the Telomerase Reverse Transcriptase (hTERT) as a
Widely Expressed Tumor Associated Antigen 8
1.7 Linking Cancer Genomics to Cancer Immunotherapy 10
1.8 Prospects for Additional Universal Tumor Antigens 11
1.9 Prospect of Universal Tumor Antigens as a Clinical Target for
Immunotherapy 11
1.10 Conclusions 12
References 13
2 Serological Determinants On Tumor Cells 17
Carsten Zwick, Klaus Dieter Preuss, Claudia Bormann,
Frank Neumann and Michael Pfreundschuh
2.1 Introduction 17
2.2 SEREX: The Approach IS
2.3 Searching for Human Antigens by SEREX 19
2.4 Molecular Characterization of SEREX Antigens 19
2.5 Specificity of SEREX Antigens 20
2.5.1 Shared Tumor Antigens 20
2.5.2 Differentiation Antigens 21
VIIII Contents
2.5.3 Antigens Encoded by Mutated Genes 21
25 A Viral Genes 22
2.5.5 Antigens Encoded by Over expressed Genes 22
2.5.6 Amplified Genes 22
2.5.7 Splice Variants of Known Genes 22
2.5.8 Cancer Related Autoantigens 22
2.5.9 Non Cancer Related Autoantigens 23
2.5.10 Products of Underexpressed Genes 23
2.6 Incidence of Antibodies to SEREX Antigens and Clinical Significance 23
2.7 Functional Significance of SEREX Antigens 24
2.8 Reverse T Cell Immunology 24
2.9 Towards a Definition of the Human Cancer Immunome 24
2.10 Consequences for Cancer Vaccine Development 25
2.11 Conclusions and Perspectives 26
References 27
3 Processing and Presentation of Tumor associated Antigens 30
Peter M. Kloetzel and Alice Sijts
3.1 The Major Histocompatibility Complex (MHC) Class I Antigen Proces¬
sing Pathway 30
3.2 Immuno Proteasomes 31
3.2.1 The Function of Immuno Proteasomes 31
3.2.2 The Role of the Proteasome Activator PA28 in Antigen Processing 33
3.3 The Proteasome System and Tumor Antigen Presentation 34
3.3.1 Impaired Epitope Generation by Immuno Proteasomes 35
3.4 PA28 and Tumor Epitope Processing 35
3.5 Exploiting Proteasome Knowledge 36
References 37
4 T Cells In Tumor Immunity 40
Pedro Romero, Mikael J. Pittet, Alfred Zippelius, Danielle Lienard,
Ferdy J. Lejeune, Danila Valmori, Daniel E. Speiser and
Jean Charles Cerottini
4.1 Introduction 40
4.2 Morphological Evidence of T Cell Immunity in Human Tumors 41
4.3 Approaches to the Molecular Identification of Cytolytic T Lymphocyte
(CTL) defined Tumor Antigens 41
4.4 Monitoring the Spontaneous CTL Responses to Tumor Antigens 44
4.4.1 Monitoring Specific CTL in the PBMC Compartment 44
4.4.2 Evidence of Tumor Antigen specific T Cell Responses
at the Tumor Sites 46
4.5 CD4 T Cells in Tumor Immunity 49
4.6 Concluding Remarks 51
References 52
Contents IIX
Part 2 Immune Evasion and Suppression 57
5 Major Histocompatibility Complex Modulation and Loss 59
Barbara Seliger and Ulrike Ritz
5.1 The Major Histocompatibility Complex (MHC) Antigen Processing
and Presentation Pathways 59
5.1.1 The MHC Class I Antigen Processing Machinery (APM) 60
5.1.2 The MHC Class II APM 61
5.2 The Physiology of the Non classical HLA G Molecule 63
5.3 Determination of the Expression of Classical and Non dassical
MHC Antigens 63
5.4 Interaction between Tumor and the Immune System 65
5.5 The Different MHC Class I Phenotypes and their Underlying Molecular
Mechanisms 66
5.5.1 MHC Class I Loss 67
5.5.2 MHC Class I Down regulation 69
5.5.3 Selective Loss or Down regulation 72
5.6 MHC Class I Alterations: Impact on Immune Responses
and Clinical Relevance 76
5.7 The Role of MHC Class II Processing and Presentation in Tumors 79
5.7.1 Frequency and Clinical Impact of MHC Class II Expression
on Tumors 79
5.7.2 Molecular Mechanisms of Deficiencies in the MHC class II APM 81
5.7.3 Modulation of Immune Response by Altered MHC Class II
Expression 81
5.7.4 MHC Class II Expression in Antitumor Response 82
5.8 Role of IFN y in Immunosurveillance 83
5.8.1 IFN y dependent Immunosurveillance of Tumor Growth 84
5.8.2 Deficiencies in the IFN Signal Transduction Pathway 85
5.9 HLA G Expression: an Immune Privilege for Malignant Cells? 85
5.9.1 HLA G Expression in Tumor Cells of Distinct Origin 86
5.9.2 Clinical Impact of HLA G Expression 88
5.9.3 Induction of Tolerance by HLA G Expression 88
5.10 Conclusions 88
Acknowledgments 89
References 89
6 Immune Cells in the Tumor Microenvironment 95
Theresa L. Whiteside
6.1 Introduction 95
6.2 The Immune System and Tumor Progression 95
6.3 Immune Cells in the Tumor Microenvironment 97
6.4 Phenotypic and Functional Characteristics of Immune Cells Present
at the Tumor Site 99
6.4.1 T Cells 99
xl Contents
6.4.2 Natural Killer (NK) Cells 201
6.4.3. DCs 105
6.4.4 Macrophages 107
6.4.5 B Cells 108
6.5 Mechanisms Linked to Dysfunction of Immune Cells in Cancer 108
6.5.1 The CD95 CD95 Ligand (CD95L) Pathway 110
6.5.2 T Lymphocyte Apoptosis in Patients with Cancer 111
6.5.3 Tumor Sensitivity to FasL Mediated Signals 111
6.5.4 A Dual Biologic Role of FasL 112
6.5.5 Contributions of other Pathways to Lymphocyte Demise in Cancer 112
6.6 Conclusions 113
References 115
7 Immunosuppressive Factors in Cancer 119
Richard Bucala and Christine N. Metz
7.1 Introduction 119
7.1 Transforming Growth Factor (TGF) (3 119
7.1.1 Sources of TGF P 121
7.1.2 Effects of TGF P 121
7.1.2.1 Effects of TGF P on monocytes/macrophages 121
7.1.2.2 Effects of TGF P on T lymphocytes 122
7.1.2.3 Effects of TGF P on NK and lymphokine activated killer (LAK)
activity 123
7.1.2.4 Effects ofTGF l;b on dendritic cells (DCs) 123
7.1.3 Inhibition of TGF P: Implications for Therapy 124
7.2 IL 10 125
7.2.1 Sources of IL 10 125
7.2.2 Effects of IL 10 226
7.2.2.1 Effects of IL 10 on monocytes/macrophages 226
7.2.2.2 Effects of IL 10 on T lymphocytes 226
7.2.2.3 Effects of IL 10 on NK cells 228
7.2.2.4 Effects of IL 10 on DCs 228
7.2.3 Inhibition of IL 10: Implications for Therapy 128
7.2.3.1 Antibodies 129
7.2.3.2 Drugs 229
7.2.3.3 Removal of the source of IL 10 229
7.3 Macrophage Migration Inhibitory Factor (MIF) 230
7.4 Prostaglandin (PG) Ez 232
7.4.1 Sources of PGE2 231
7.4.2 Effects of PGE2 232
7.4.2.1 Effects of PGE2 on monocytes/macrophages 232
7.4.2.2 Effects of PGE2 on T lymphocytes 23 2
7.4.2.3 Effects of PGE2 on NK cells and LAK activity 132
7.43 Inhibition of PGE2: Implications for Therapy 232
7.5 Polyamines 232
Contents XI
7.5.1 Sources of Polyamines 133
7.5.2 Effects of Polyamines 133
7.5.2.1 Effects of polyamines on monocytes/macrophages 133
7.5.2.2 Effects of polyamines on T lymphocytes 134
7.5.2.3 Effects of polyamines on NK cells 134
7.5.3 Inhibition of Polyamine Biosynthesis: Implications for Therapy 134
7.6 Tumor Shed Immunosuppressive Molecules 134
7.7 Conclusion 135
References 136
8 lnterleukin 10 in Cancer Immunity 155
Robert Sabat and Khusru Asadullah
8.1 Introduction 155
8.2 IL 10 Protein and IL 10 Receptor (IL 10R) 155
8.2.1 IL 10 Structure and Expression 155
8.2.2 IL 10R 256
8.2.3 IL 10 Homologs 157
8.3 Biological Activities of IL 10 157
8.3.1 Effects on Myeloid Antigen Presenting Cells (APC) 158
8.3.2 Effects on T Cells 159
8.3.3 Effects on Natural Killer (NK) Cells 160
8.3.4 Effects on other Immune Cells 160
8.3.5 IL 10 s Role in the Immune System 260
8.4 IL 10 Expression in Cancer Patients 161
8.4.1 Cellular Sources of IL 10 in Cancer Patients 162
8.4.2 Selectivity of IL 10 Production 162
8.4.3 IL 10 Presence: Local or Systemic? 163
8.4.4 Prognostic Value of Enhanced IL 10 Expression 263
8.5 Effects of IL 10 in Cancer Models 164
8.5.1 Tumor Promoting Effects of IL 10 264
8.5.2 Tumor Inhibiting Effects of IL 10 265
8.6 Conclusions 166
Acknowledgements 267
References 268
Part 3 Strategies for Cancer Immunology 277
9 Dendritic Cells and Cancer: Prospects for Cancer Vaccination 279
Derek N. J. Hart, David Jackson and Frank Nestle
9.1 Introduction 179
9.2 DC Properties 279
9.3 DC in Human Cancer 282
9.4 Blood DC Counts and DC Mobilization 283
9.5 DC Preparations for Immunotherapy 284
XII I Contents
9.6 Loading DC with Antigens 186
9.7 Dose Delivery and Vaccination Schedule 187
9.8 Phase I/II Clinical Trials 188
9.9 Phase III Clinical Trials 193
9.10 Side Effects 194
9.11 Monitoring Immune Responses 194
9.12 Tumor Escape 195
9.13 New Developments in DC Immunotherapy 196
9.14 Conclusion 197
References 197
10 The Immune System in Cancer: If It Isn t Broken, Can We Fix It? 204
Richard G. Vile
10.1 Commitment and the Modern Immune System 204
10.2 Evolutionary Tuning 206
10.3 Tumor Antigens and Responses to Them 209
10.4 Antigen Presentation A Resume 209
10.5 Playing to Strengths 211
10.6 Exploiting Weaknesses: Autoirnmunity 214
10.7 Combining the Best of Both Worlds 218
10.8 The Way Forward 221
Acknowledgments 223
Appendix: Glossary 223
References 225
11 Hybrid Cell Vaccination for Cancer Immune Therapy 230
Peter Walden, Gernot Stuhler and Uwe Trefzer
11.1 Introduction 230
11.2 Immunological Basis of the HCV Approach to Cancer Immune
Therapy 231
11.2.1 Tumor Antigenicity 231
11.2.2 T T Cell Collaboration in the Induction of Cellular Cytotoxic Immune
Responses 233
11.3 Vaccination Strategies for Cancer Immune Therapy 235
11.4 HCV 236
11.4.1 Conceptual Basis 236
11.4.2 HCV in Preclinical Studies 237
11.4.3 Clinical Experience with HCV 238
11.5 Conclusion and Prospects 240
References 241
12 Principles and Strategies Employing Heat Shock Proteins
for Immunotherapy of Cancers 253
ZlHAI Li
12.1 The Thesis 253
Contents I XIII
12.1.1 HSPs per se are rarely Tumor Antigens 254
12.1.2 HSPs are Molecular Chaperones for Antigenic Peptides 254
12.1.3 HSPs are Adjuvants 255
12.1.4 HSPs are Involved in Cross Priming 255
12.1.5 Other Roles 256
12.2 Cancer Immunotherapy Strategies with HSPs 256
12.2.1 Strategy l:Autologous HSPs as Tumor Specific Vaccines 256
12.2.2 Strategy 2: HSPs as Adjuvant 258
12.2.2.1 Non covalent complex between HSP and antigenic peptides 259
12.2.2.2 Covalent complex between HSP and antigenic peptides 259
12.2.3 Strategy 3: Whole Cell Vaccine based on the Modulation
of the Expression of HSPs 260
12.2.3.1 Modulation of the level of HSPs for cancer immunotherapy 261
12.2.3.2 Modulation of the site of HSP expression for cancer
immunotherapy 262
12.3 Conclusion and Perspectives 263
References 264
13 Applications of CpG Motifs from Bacterial DNA in Cancer
Immunotherapy 26S
Arthur M. Krieg
13.1 History of Cancer Immunotherapy with Bacterial Extracts and Nucleic
Acids 268
13.2 CpG Motifs in bDNA Explain its Immune Stimulatory Activity 270
13.3 Identification of a Specific Receptor for CpG motifs, Toll like Receptor
(TLR) 9 271
13.4 Backbone dependent Immune Effects of CpG Motifs and Delineation of
CpG A versus CpG B Classes of ODN 272
13.5 Applications of CpG DNA in Immunotherapy of Cancer 274
13.5.1 CpG A or CpG B DNA as a Monotherapy 274
13.5.2 CpG DNA as an Adjuvant for Cancer Vaccines 276
13.5.3 Application of CpG DNA to Enhance ADCC for Treating Cancer 277
13.6 Conclusion 278
Acknowledgments 278
References 279
14 The T Body Approach: Towards Cancer Immuno Gene Therapy 287
Jehonathan H. Pinthus and Zeiig Eshhae
14.1 Background 287
14.2 CRs with Antitumor Specificity 288
14.2.1 Optimizing the CR Design 288
14.2.1.1 The single chain CR 288
14.2.1.2 Direct recruitment of intracellular triggering molecules 288
14.2.1.3 Combining stimulatory and co stimulatory signals 289
14.2.2 Anticancer Specificities of CRs 290
XIV I Contents
14.2.2.1 Cancer specific antibodies 290
14.2.2.2 Ligands and receptors recognition units 290
14.2.3. Pre Clinical Experimental Models 292
14.2.4. Clinical Trials 293
14.3 Conclusions and Perspectives 294
Acknowledgments 295
References 295
15 Bone Marrow Transplantation for Immune Therapy 299
Fabio Ciceri and Claudio Bordignon
15.1 Introduction 299
15.2 Graft versus Host (GvH) Reactions 299
15.3 Graft versus Tumor (GvT) Effect 301
15.4 Donor Lymphocyte Infusions (DLIs) 301
15.5 Complications of DLI: GvHD and Marrow Aplasia 303
15.6 Strategies to reduce GvHD while preserving GvT 303
15.7 The Suicide Gene Strategy 304
15.8 HSV tfc Lymphocyte Add backs after Haploidentical Transplantation 306
15.9 Reduced Intensity versus Conventional Conditioning Regimens 307
References 307
16 Immunocytokines: Versatile Molecules for Biotherapy
of Malignant Disease 311
Holger N. Lode, Rong Xiang, Jurgen C. Becker, Andreas G. Niet
hammer, F. James Primus, Stephen D. Gillies and Ralph A. Reiseeld
16.1 Introduction 311
16.1.1 Immunocytokines 311
16.1.2 Construction of Immunocytokines 312
16.1.3 Binding and Cytokine Activity of IL 2 Immunocytokines 313
16.2 Treatment of Tumor Metastases with Immunocytokines 313
16.2.1 Colorectal Carcinoma 313
16.2.2 Long lived Tumor Protective Immunity is Boosted by Non curative Doses
of huKSl/4 IL 2 Immunocytokine 316
16.2.3 Carcinoembryonic Antigen (CEA) based DNA Vaccines for Colon
Carcinoma Boosted by IL 2 Immunocytokine 319
16.2.4 T Cell mediated Protective Immunity against Colon Carcinoma Induced
by a DNA Vaccine encoding CEA and CD40 Ligand Trimer
(CD40LT) 322
16.3 Non small Cell Lung Carcinoma 324
16.3.1 Boost of a CEA based DNA Vaccine by the huKS 1/4 IL 2 Immuno¬
cytokine 324
16.4 Prostate Carcinoma 327
Id A.I Suppression of Human Prostate Cancer Metastases by an IL 2
Immunocytokine 327
16.5 Melanoma 330
Contents I XV
16.5.1 Treatment of Tumor Metastases with Immunocytokines 330
16.5.2 Tumor Targeting of LT a Induces a Peripheral Lymphoid like Tissue
Leading to an Efficient Immune Response against Melanoma 333
16.5.3 chl4.18 IL 2 Immunocytokine Boosts Protective Immunity Induced
by an Autologous Oral DNA Vaccine against Murine Melanoma 334
16.6 Neuroblastoma 337
16.6.1 Treatment with chl4.18 IL 2 Immunocytokine 337
16.6.2 Immunocytokine Treatment of Bone Marrow and Liver Metastases 337
16.6.3 Mechanism of Immunocytokine mediated Immune Responses 338
16.6.4 Amplification of Suboptimal CD8+ T Memory Cells by a Cellular
Vaccine 340
16.6.5 Synergy between Targeted IL 2 and Antiangiogensis 341
16.7 Conclusions and Perspectives 342
Acknowledgments 342
References 343
17 Immunotoxins and Recombinant Immunotoxins in Cancer Therapy 347
Yoram Reiter and Avital Lev
17.1 Introduction 347
17.2 First and Second Generation Immunotoxins 350
17.3 The Development of Recombinant DNA based Immunotoxins: Design of
Recombinant Immunotoxins 351
17.3.1 The Toxin Moiety 351
17.3.1.1 Plant toxins 351
17.3.1.2 Bacterial toxins: DTand DT derivatives 352
17.3.1.3 Bacterial toxins: PE and PE derivatives 353
17.3.2 The Targeting Moiety Recombinant Antibody Fragments 354
17.4 Construction and Production of Recombinant Immunotoxins 357
17.5 Predinical Development of Recombinant Immunotoxins 358
17.6 Application of Recombinant Immunotoxins 360
17.6.1 Recombinant Immunotoxins against Solid Tumors 360
17.6.2 Recombinant Immunotoxins against Leukemias and Lymphomas 361
17.7 Isolation of New and Improved Antibody Fragments as Targeting
Moieties: Display Technologies for the Improvement of Immunotoxin
Activity 363
17.8 Improving the Therapeutic Window of Recombinant Immunotoxins:
The Balance of Toxicity, Immunogenicity and Efficacy 366
17.8.1 Immune Responses and Dose limiting Toxicity 367
17.8.2 Specificity Dictated by the Targeting Moiety 368
17.9 Conclusions and Perspectives 369
References 369
Glossary 380
Index 395
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV014686197 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T19:05:03Z |
| institution | BVB |
| isbn | 352730441X |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009960072 |
| oclc_num | 48627431 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-188 DE-578 |
| owner_facet | DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-188 DE-578 |
| physical | XXVI, 408 S. Ill., graph. Darst. |
| publishDate | 2002 |
| publishDateSearch | 2002 |
| publishDateSort | 2002 |
| publisher | Wiley-VCH |
| record_format | marc |
| spelling | Cancer immune therapy current and future strategies ed. by G. Stuhler ... Weinheim Wiley-VCH 2002 XXVI, 408 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Cancer - Immunothérapie Tumeurs - Immunologie Cancer Immunotherapy Immunotherapy Neoplasms therapy Tumors Immunological aspects Krebs Medizin (DE-588)4073781-0 gnd rswk-swf Immuntherapie (DE-588)4026640-0 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Krebs Medizin (DE-588)4073781-0 s Immuntherapie (DE-588)4026640-0 s DE-604 Stuhler, Gernot Sonstige (DE-588)11501621X oth HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009960072&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Cancer immune therapy current and future strategies Cancer - Immunothérapie Tumeurs - Immunologie Cancer Immunotherapy Immunotherapy Neoplasms therapy Tumors Immunological aspects Krebs Medizin (DE-588)4073781-0 gnd Immuntherapie (DE-588)4026640-0 gnd |
| subject_GND | (DE-588)4073781-0 (DE-588)4026640-0 (DE-588)4143413-4 |
| title | Cancer immune therapy current and future strategies |
| title_auth | Cancer immune therapy current and future strategies |
| title_exact_search | Cancer immune therapy current and future strategies |
| title_full | Cancer immune therapy current and future strategies ed. by G. Stuhler ... |
| title_fullStr | Cancer immune therapy current and future strategies ed. by G. Stuhler ... |
| title_full_unstemmed | Cancer immune therapy current and future strategies ed. by G. Stuhler ... |
| title_short | Cancer immune therapy |
| title_sort | cancer immune therapy current and future strategies |
| title_sub | current and future strategies |
| topic | Cancer - Immunothérapie Tumeurs - Immunologie Cancer Immunotherapy Immunotherapy Neoplasms therapy Tumors Immunological aspects Krebs Medizin (DE-588)4073781-0 gnd Immuntherapie (DE-588)4026640-0 gnd |
| topic_facet | Cancer - Immunothérapie Tumeurs - Immunologie Cancer Immunotherapy Immunotherapy Neoplasms therapy Tumors Immunological aspects Krebs Medizin Immuntherapie Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009960072&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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