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More About This Title Viral Therapy of Cancer
English
This book provides a comprehensive yet succinct overview of the current status of viral therapy of cancer. Chapters coherently present the advances made with individual agents and review the biological and clinical background to a range of viral therapies: structured to proceed from basic science at the bench to the patient’s bedside, they give an up-to-date and realistic evaluation of a therapy’s potential utility for the cancer patient.
- Presents state of the art knowledge on how viruses can be, and have been, used in novel therapeutic approaches for the treatment of cancer
- Describes the use of viruses as oncolytic agents, killing cells directly
- Editors are experts in the field, with experience of both laboratory and clinical research
Viral Therapy of Cancer is essential reading for both basic scientists and clinicians with an interest in viral therapy and gene therapy.
English
Dr K. J. Harrington, Targeted Therapy Laboratory, Cancer Research UK, Centre for Cell and Molecular Biology, Institute of Cancer Research, London, UK.
Dr H. S. Pandha, Department of Medical Oncology, St. George's Hospital Medical School, London, UK.
Professor R. G. Vile, Molecular Medicine Program,?Mayo Clinic, Rochester, USA.
English
Foreword xiii
Preface xv
Contributors xvii
1 Adenoviruses 1
Kate Relph, Kevin J. Harrington, Alan Melcher and Hardev S. Pandha
1.1 Introduction 1
1.2 Viral structure and life cycle 1
1.3 Adenoviral vectors 5
1.4 Targeting adenoviral vectors 6
1.5 Clinical applications of adenoviral gene therapy 7
1.6 Adenoviral vectors for immunotherapy 7
1.7 Adenoviral vectors for suicide gene therapy 10
1.8 Adenoviral vectors for gene replacement therapy 11
1.9 Oncolytic adenoviral therapy 12
1.10 Adverse outcomes of adenoviral gene therapy 13
1.11 Summary 13
References 14
2 Application of HSV-1 vectors to the treatment of cancer 19
Paola Grandi, Kiflai Bein, Costas G. Hadjipanayis, Darren Wolfe, Xandra O. Breakefield and Joseph C. Glorioso
2.1 Introduction 19
2.2 Basic biology of HSV 19
2.3 Replication competent or oncolytic vectors 24
2.4 Replication defective vectors 28
2.5 Amplicons 30
2.6 Impediments to the efficacy of HSV vectors for cancer gene therapy 32
2.7 Strategies to enhance the efficacy and specificity of HSV vectors for cancer gene therapy 36
2.8 Summary and conclusions 42
Acknowledgements 42
References 42
3 Adeno-associated virus 55
Selvarangan Ponnazhagan
3.1 Introduction 55
3.2 Biology and life cycle of AAV 55
3.3 AAV serotypes 57
3.4 Production of recombinant AAV 57
3.5 Gene therapy for cancer treatment 57
3.6 Anti-oncogenic properties of AAV 58
3.7 Molecular chemotherapy studies with rAAV 59
3.8 AAV-mediated sustained transgene expression as a potential cancer gene therapy strategy 59
3.9 rAAV vectors have advantages in stimulating T helper 1/cytotoxic T lymphocyte responses 60
3.10 rAAV vectors can be used to initiate immune responses 61
3.11 Altering AAV tropism for tumour-specific delivery 62
3.12 Clinical trials involving rAAV 62
3.13 Conclusion 63
Acknowledgements 63
References 63
4 Retroviruses 69
Simon Chowdhury and Yasuhiro Ikeda
4.1 Introduction 69
4.2 Structure of retroviral particles 69
4.3 Retroviral genome 69
4.4 Retroviral life cycle 70
4.5 Retroviral vectors 71
4.6 Safety of retroviral vectors: insertional mutagenesis 72
4.7 Gene therapy of X-linked SCID 72
4.8 Retroviral cancer gene therapy 75
4.9 Immunomodulatory approaches 78
4.10 Conclusions 79
References 80
5 Lentiviral vectors for cancer gene therapy 83
Antonia Follenzi and Elisa Vigna
5.1 Development of lentiviral vectors (LV) 83
5.2 Targeting of transgene expression 85
5.3 Host immune responses to LV and their transgene 86
5.4 Transgenesis 87
5.5 Haematopoietic stem cell gene transfer 87
5.6 Cancer treatment by LV 89
5.7 Approved clinical trials using LV 91
5.8 Conclusions 91
References 91
6 Poxviruses as immunomodulatory cancer therapeutics 95
Kevin J. Harrington, Hardev S. Pandha and Richard G. Vile
6.1 Introduction 95
6.2 General features of poxvirus structure and biology 95
6.3 Clinically applicable poxviruses 97
6.4 Poxviruses as potential cancer therapeutics 99
6.5 Clinical experience with poxviruses 102
6.6 Conclusions 110
References 110
7 Oncolytic herpes simplex viruses 115
Guy R. Simpson and Robert S. Coffin
7.1 Introduction 115
7.2 Herpes simplex virology 115
7.3 Properties of HSV relevant to oncolytic virus therapy 117
7.4 Mutations giving tumour-selective replication 118
7.5 Oncolytic HSV expressing fusogenic membrane glycoproteins (FMG) 125
7.6 Prodrug activation therapy and oncolytic HSV 126
7.7 Combination of oncolytic HSV with immunomodulatory gene expression 127
7.8 Combination of conventional therapies with oncolytic HSV 128
7.9 Summary 129
Acknowledgement 130
References 130
8 Selective tumour cell cytotoxicity by reoviridae – preclinical evidence and clinical trial results 139
Laura Vidal, Matt Coffey and Johann de Bono
8.1 Introduction 139
8.2 Reovirus structure 139
8.3 Reovirus replication 140
8.4 Reovirus and human infection 141
8.5 Oncolytic activitiy 142
8.6 Mechanism of reovirus-induced cytotoxicity 145
8.7 Preclinical experience 145
8.8 Immunogenicity 146
8.9 Clinical experience 146
8.10 Conclusions 147
References 148
9 Oncolytic vaccinia 151
M. Firdos Ziauddin and David L. Bartlett
9.1 Introduction 151
9.2 Biology of vaccinia virus 151
9.3 Tumour selectivity and antitumour effect 153
9.4 Improving antitumour effects through bystander effects 160
9.5 Immune response to vaccinia and vaccinia immune evasion strategies 161
9.6 Virus-driven antitumour immune response 163
9.7 Imaging 164
9.8 Current and potential clinical applications 165
References 166
10 Newcastle Disease virus: a promising vector for viral therapy of cancer 171
Volker Schirrmacher and Philippe Fournier
10.1 Introduction 171
10.2 Structure, taxonomy, pathogenicity and oncolytic properties of NDV 171
10.3 Human application and safety 172
10.4 Tumour-selective replication of NDV 174
10.5 Virally based cancer immunotherapy and danger signals 174
10.6 NDV: a danger signal inducing vector 175
10.7 The human cancer vaccine ATV-NDV 176
10.8 Pre-existing antitumour memory T cells from cancer patients and their activation by antitumour vaccination with ATV-NDV 177
10.9 Clinical trials of antitumour vaccination with ATV-NDV 177
10.10 NDV-specific recombinant bispecific antibodies to augment antitumour immune responses 179
10.11 NDV-binding bispecific fusion proteins to improve cancer specific virus targeting 180
10.12 Recombinant NDV as a new vector for vaccination and gene therapy 180
10.13 Conclusion 181
References 182
11 Vesicular stomatitis virus 187
John Bell, Kelly Parato and Harold Atkins
11.1 Introduction 187
11.2 VSV: genomic organization and life cycle 187
11.3 Host range and pathogenesis of VSV infection 188
11.4 Control of VSV infection by the innate type I interferon response 189
11.5 Cancer cells are insensitive to type I interferon 190
11.6 VSV preferentially replicates in and lyses tumour cells in vitro 190
11.7 VSV attenuation: enhanced tumour selectivity and therapeutic index 192
11.8 Engineered/recombinant VSV 192
11.9 VSV effectively eradicates tumours in vivo 193
11.10 VSV and the host immune response 194
11.11 Host immunity vs. therapeutic efficacy 195
11.12 VSV is a potent vaccine 195
11.13 Innate sensing of VSV and the antitumour response 196
11.14 So what is a good oncolytic virus? 197
11.15 Future challenges for VSV 198
References 199
12 Measles as an oncolytic virus 205
Adele Fielding
12.1 Introduction 205
12.2 Measles virus and the consequences of natural infection 205
12.3 MV vaccine 206
12.4 MV genetics and engineering 206
12.5 MV receptors 207
12.6 Animal models for the study of MV pathogenesis and oncolysis 207
12.7 Oncolytic activity of MV 208
12.8 Mechanism of specificity 208
12.9 Targeting MV entry 209
12.10 Enhancing the oncolytic activity of MV 210
12.11 Interactions with the immune system 210
12.12 Potential specific toxicities of clinical use of replicating attenuated MV 211
12.13 Clinical trials 211
12.14 Conclusions 212
References 212
13 Alphaviruses 217
Ryuya Yamanaka
13.1 Introduction 217
13.2 RNA viruses as gene expression vectors 218
13.3 The biology of alphaviruses 218
13.4 Heterologous gene expression using alphavirus vectors 220
13.5 Cancer gene therapy strategies using alphavirus vectors 221
13.6 Alphavirus vector development for gene therapy application 223
13.7 Conclusions 224
References 225
14 Tumour-suppressor gene therapy 229
Bingliang Fang and Jack A. Roth
14.1 Tumour-suppressor genes 229
14.2 Use of tumour-suppressing genes for cancer therapy 231
14.3 Clinical trials of p53 gene replacement 232
14.4 Tumour-suppressor gene therapy in multimodality anticancer treatment 233
14.5 Future prospects 235
Acknowledgements 235
References 236
15 RNA interference and dominant negative approaches 241
Charlotte Moss and Nick Lemoine
15.1 Introduction 241
15.2 Oligonucleotide agents 241
15.3 Mechanism of RNAi 242
15.4 RNAi and antisense compared 243
15.5 siRNA design 244
15.6 Off-target effects 244
15.7 Induction of innate immunity 246
15.8 Methods of delivery 247
15.9 Antisense 251
15.10 Dominant negative approaches 252
15.11 Research applications of siRNA 252
15.12 Therapeutic applications of siRNA 252
References 253
16 Gene-directed enzyme prodrug therapy 255
Silke Schepelmann, Douglas Hedley, Lesley M. Ogilvie and Caroline J. Springer
16.1 Introduction 255
16.2 Enzyme-prodrug systems for GDEPT 255
16.3 Gene delivery vectors for GDEPT 262
16.4 Conclusions 268
References 269
17 Immunomodulatory gene therapy 277
Denise Boulanger and Andrew Bateman
17.1 Introduction 277
17.2 Immunotherapy strategies using viral vectors 277
17.3 Viruses used as viral vectors in cancer immunotherapy 280
17.4 Clinical trials against specific TAA 283
17.5 Conclusions and future prospects 289
References 290
18 Antiangiogenic gene delivery 295
Anita T. Tandle and Steven K. Libutti
18.1 Angiogenesis: role in tumour development and metastasis 295
18.2 Targeting tumour vasculature as an approach for cancer treatment 297
18.3 Viral vectors to deliver antiangiogenic gene products 299
18.4 Viral targeting 303
18.5 Concluding remarks 306
References 306
19 Radiosensitization in viral gene therapy 313
Jula Veerapong, Kai A. Bickenbach and Ralph R. Weichselbaum
19.1 Introduction 313
19.2 Adenovirus 313
19.3 Adeno-associated viruses 314
19.4 Herpes simplex viruses 314
19.5 Enhancing the effect of radiation by delivering tumour suppressor genes 316
19.6 Virus-directed enzyme prodrug therapy 316
19.7 Conclusions 322
References 324
20 Radioisotope delivery 327
Inge D.L. Peerlinck and Georges Vassaux
20.1 Introduction 327
20.2 History of iodine therapy 327
20.3 Genetic therapy 330
20.4 Conclusion 338
References 338
21 Radioprotective gene therapy: current status and future goals 341
Joel S. Greenberger and Michael W. Epperly
21.1 Introduction 341
21.2 Organ-specific radiation protection: oral cavity/oropharynx 342
21.3 MnSOD-PL treatment reduces pulmonary irradiation damage 354
21.4 MnSOD-PL gene therapy down-modulates marrow cell migration to the lungs 357
21.5 MnSOD-PL systemic administration for radiation protection from TBI 358
21.6 Summary and future directions 359
References 360
22 Chemoprotective gene delivery 377
Michael Milsom, Axel Schambach, David Williams and Christopher Baum
22.1 Introduction 377
22.2 The promise of chemoselection strategies 377
22.3 The limitations of chemoselection strategies 381
22.4 Which expression level of chemoprotective genes is appropriate? 384
22.5 Vector design to achieve optimal expression levels 385
22.6 Exploring side effects of continued transgene expression and insufficient chemoprotection 387
22.7 The future: inducible expression of drug resistance genes 388
Acknowledgements 389
References 389
Index 393
