: Jack A. Roth
: Jack A. Roth
: Gene-Based Therapies for Cancer
: Springer-Verlag
: 9781441961020
: 1
: CHF 132.60
:
: Nichtklinische Fächer
: English
: 278
: Wasserzeichen/DRM
: PC/MAC/eReader/Tablet
: PDF
Cancer gene therapy is a novel therapy that targets the underlying genetic defects in the cancer cell. Progress in this field has been rapid and gene therapy promises to further extend personalized cancer treatment. In this volume leading experts have contributed their experience in developing gene therapies for a variety of cancers. Translational gene therapy approaches are emphasized. Chapters include discussions of specific gene delivery technologies as well as their application to various cancers with extensive discussions of ongoing clinical trials. This information should be useful to both students, fellows, and experienced scientists with an interest in this rapidly developing area.
Foreword6
Contents8
Contributors10
Chapter 1: RNAi: A New Paradigm in Cancer Gene Therapy16
1 Introduction17
2 Clinical Significance of the RNAi Processing Machinery18
3 Clinical Application of RNAi19
4 Off-Target Effects23
5 RNAi Imaging: Biodistribution and Target Modulation25
6 Development of RNAi-Based Gene Therapy: Clinical Trials26
7 Future Development27
References28
Chapter 2: Gene-Based Therapy for Cancer: Brain Tumors31
1 Introduction31
2 Replication-Deficient Viral Vectors32
2.1 Ad-p5332
2.2 HSVtk/GCV Gene Therapy34
3 Oncolytic Viruses35
3.1 Adenovirus35
3.1.1 ONYX-01536
3.1.2 Delta-24-RGD37
3.2 Herpes Simplex Virus-138
3.3 Reovirus39
3.4 Measles Virus40
3.5 Newcastle Disease Virus40
4 Future Perspectives41
References42
Chapter 3: Gene Therapy of Prostate Cancer47
1 Introduction47
2 Enzyme/Prodrug Gene Therapy48
2.1 Enzyme/Prodrug Gene Therapy Using Replication-Defective Adenoviruses48
2.2 Enzyme/Prodrug Gene Therapy Using Replication-Competent Adenoviruses50
3 Vaccine-Based Gene Therapy Strategies55
3.1 Poxvirus-Based Vaccines55
3.2 Cell-Based Vaccines57
4 Replication-Competent, Oncolytic Adenoviruses58
5 Summary59
References60
Chapter 4: siRNA Versus shRNA for Personalized Cancer Therapy: Mechanisms and Applications64
1 Introduction65
2 Personalized Cancer Therapy65
3 Mechanisms of RNAi66
3.1 siRNA66
3.2 shRNA68
3.2.1 Bifunctional shRNA69
4 SiRNA Versus shRNA70
4.1 Comparative Efficacy70
4.2 Dicer/Drosha Expression in Cancer and RNAi Effector Suitability70
4.3 Off-Target Effects71
4.3.1 Specific Off-Target Effects71
4.3.2 Nonspecific Off-Target Effects71
5 Delivery Strategies for Clinical Translation72
6 Conclusions73
References73
Chapter 5: Tumor Suppressor Gene Therapy76
1 Tumor Suppressor Gene Therapy77
2 Gene Replacement by p53 in Laboratory Studies78
3 Clinical Trials of p53 Gene Replacement79
4 Gene Replacement in Combination with DNA Damaging Agents81
5 Clinical Trials of Tumor Suppressor Gene Replacement Combined with Chemotherapy82
6 Clinical Trials of p53 Gene Replacement Combined with Radiation Therapy82
7 Systemic Gene Therapy for Metastases84
8 Summary and Conclusions87
References88
Chapter 6: Targeted Oncolytic Adenovirus for Human Cancer Therapy: Gene-Based Therapies for Cancer92
1 Introduction92
2 Telomerase Activity for Transcriptional Cancer Targeting94
3 Telomerase-Specific Oncolytic Adenovirus for Cancer Therapeutics94
3.1 Structure of hTERT Promoter-Driven Oncolytic Adenovirus94
3.2 Preclinical Studies of hTERT Promoter-Driven Oncolytic Adenovirus95
3.3 Immune Activation by hTERT Promoter-Driven Oncolytic Adenovirus98
4 Telomerase-Specific Oncolytic Adenovirus for Cancer Diagnostics99
4.1 hTERT Promoter-Driven GFP-Expressing Oncolytic Adenovirus99
4.2 Ex vivo Imaging of Human Circulating Tumor Cells with GFP Fluorescence99
4.3 In Vivo Imaging of Lymph Node Micrometastasis with GFP Fluorescence100
5 Clinical Application of Telomerase-Specific Oncolytic Adenovirus101
6 Conclusions and Perspectives101
References103
Chapter 7: Gene Therapy for Malignant Pleural Mesothelioma107
1 Background107
2 MPM as a Target for Gene Therapy108
3 Preclinical Investigations108
3.1 Induction of Apoptosis108
3.2 Antiangiogenesis110
3.3 Suicide-Gene Therapy110
3.4 Immunogene Therapy112
3.5 Replicating, Tumor-Selective Oncolytic Viral Vectors113
4 Clinical Investigations114
4.1 Suicide Gene Therapy114
4.2 Cytokine Gene Therapy116
5 Summary118
References119
Chapter 8: Mesenchymal Stem/Stromal Cells as Cellular Vehicles for Tumor Targeting124
1 Introduction124
1.1 Tumor Cell-Centric View on Tumor Development124
1.2 Stroma is a Common Ground for Numerous Cancers125
1.3 Role of Fibroblasts and Stromal Precursors128
2 Tropism of MSC for Wounds and Tumors129
2.1 But Which Cell in the Stroma to Target130
2.2 Rationale for Targeting Tumors Using Stromal Precusor Cells131
2.3 Migratory Factors132
3 Use of Stem Cells as Cellular Vehicles to Target Tumors133
3.1 MSC as Cell Vehicles for Cancer135
4 Interferons136
5 Interleukins137
6 Conditionally Replication Adenoviral Vectors138
7 Chemokines and Growth Factor Antagonists139
8 Suicide Genes139
9 Tumor Necrosis Factor-Related Apoptosis Inducing Ligand140
10 Alternative Mesenchymal Tissues as Sources for Anticancer Therapies140
11 Conclusions141
References142
Chapter 9: Retargeting Adenovirus for Cancer Gene Therapy151
1 Introduction151
2 Adenovirus Life Cycle and Genomic Organization152
3 Strategies for Ad-Based Cancer Gene Therapy153
3.1 Cancer Gene Therapy Vectors153
3.2 Immunotherapy Vectors153
3.3 Virotherapy Vectors154
4 A Need for Retargeted Adenovirus-Based Vectors for Cancer Therapy154
5 Transductional Targeting155
5.1 Adapter-Based Targeting155
5.2 Genetic Modifications156
6 Cellular Control of Ad Vecto