Gene therapy as a treatment for cancer is at a critical point in its evolution. Exciting new developments in gene targeting and vector technology, coupled with results from the first generation of preclinical and clinical studies have led to the design and testing of new therapeutic approaches. The Third Edition of Gene Therapy of Cancer provides crucial updates on the basic and applied sciences of gene therapy. It offers a comprehensive assessment of the field including the areas of suicide gene therapy, oncogene and suppressor gene targeting, immunotherapy, drug resistance gene therapy, and the genetic modification of stem cells. Researchers at all levels of development, from basic laboratory investigators to clinical practitioners, will find this book to be instructive.
Cancer gene therapy, like cancer therapy in general, is evolving rapidly, testing new concepts, targets and pathways, evoking new technologies, and passing new regulatory hurdles. Its essence, however, has not changed: the hope and challenges of returning altered genes to normal, using targeted gene expression to alter the function of both tumor and microenvironment, and in some cases normal cells, and delivering functionally important genes to specific cell types to increase sensitivity to killing or to protect normal cells from cancer therapies.
In some instances, gene therapy for cancer forms a continuum from gene repair through the use of molecularly modified cells; the use of viral and non-viral vector based gene delivery to both tumor and tumor microenvironment; the use of viral and gene based vaccines; and development of new gene-based therapeutics. The unique mechanistically chosen vector platforms are at the heart of this technology because they allow for direct and selective cell death and transient to sustained delivery of vaccine molecules or molecules that affect the microenvironment, vasculature, or the immune response.
1. Cover image - p. Cover 2. Title page - p. Cover 3. Table of Contents - p. Cover 4. Copyright - p. Cover 5. Dedication - p. IV 6. List of Contributors - p. V 7. Section I: Viral and Nonviral Vector Methodologies: Targets and Approaches - p. V 8. Section I. Viral and Nonviral Vector Methodologies: Targets and Approaches - p. V 9. Chapter 1. Ex Vivo Gene Therapy: Utilization of Genetic Vectors for the Generation of Genetically Modified Cell Products for Therapy - p. 2 10. Chapter 2. Targeting Tumor Vasculature Using Adeno-Associated Virus Phage Vectors Coding Tumor Necrosis Factor-α - p. 12 11. Chapter 3. Viral Insertion Site Detection and Analysis in Cancer Gene Therapy - p. 30 12. Chapter 4. Targeted Systemic Delivery of Therapeutic siRNA - p. 45 13. Chapter 5. Bacterial Delivery of RNAi Effectors - p. 63 14. Chapter 6. Gene-Directed Enzyme Prodrug Cancer Therapy - p. 74 15. Chapter 7. Electroporation Gene Therapy - p. 87 16. Chapter 8. Toxin-Based Cancer Gene Therapy: Under the Control of Oncofetal H19 Regulatory Sequences - p. 103 17. Chapter 9. Gene Therapy in Radiotherapy of Cancer - p. 120 18. Section II: Oncolytic Viruses - p. 129 19. Section II. Oncolytic Viruses - p. 129 20. Chapter 10. Advances in Oncolytic Virotherapy for Brain Tumors - p. 136 21. Chapter 11. Oncolytic Adenoviruses in the Treatment of Cancer in Humans - p. 147 22. Chapter 12. Selectively Replicating Oncolytic Adenoviruses Combined with Chemotherapy, Radiotherapy, or Molecular Targeted Therapy for Treatment of Human Cancers - p. 167 23. Chapter 13. Reoviral Therapy for Cancer: Strategies for Improving Antitumor Efficacy Using Radio- and Chemotherapy - p. 180 24. Chapter 14. Selectively Replicating Herpes Simplex Viral Vectors - p. 196 25. Chapter 15. Modified Oncolytic Herpesviruses for Gene Therapy of Cancer - p. 209 26. Chapter 16. The Lister Strain of Vaccinia Virus as an Anticancer Therapeutic Agent - p. 222 27. Section III: Immunotherapeutics - p. 235 28. Section III. Immunotherapeutics - p. 235 29. Chapter 17. Poxvirus-Based Strategies for Combined Vaccine and Tumor Microenvironment Manipulation - p. 240 30. Chapter 18. Genetically Engineered (T Cell Receptor) T Cells for Adoptive Therapy - p. 254 31. Chapter 19. Genetically Modified Dendritic Cell Vaccines for Solid Tumors - p. 266 32. Chapter 20. Dendritic Cell Vaccination - p. 280 33. Chapter 21. Chemokine Gene-Modified Dendritic Cells for Cancer Therapy - p. 295 34. Chapter 22. The Use of T Cell Costimulation to Enhance the Immunogenicity of Tumors - p. 312 35. Chapter 23. Clinical Application of Plasmid-Based Cancer Vaccines - p. 332 36. Chapter 24. Lentivector Vaccines - p. 341 37. Chapter 25. Therapeutic Efficacy and Systemic Antitumor T Cell Immunity Induced by RheoSwitch-Regulated IL-12 Expression after Intratumoral Injection of Adenovirus Vector or Vector-Transduced Dendritic Cells - p. 357 38. Section IV: Drug Resistance and Metabolism Gene Therapy - p. 373 39. Section IV. Drug Resistance and Metabolism Gene Therapy - p. 373 40. Chapter 26. Clinical Trials Using LV-P140K-MGMT for Gliomas - p. 378 41. Chapter 27. RNA Interference Therapeutics for Tumor Therapy: Promising Work in Progress - p. 387 42. Chapter 28. MGMT Stem Cell Selection and Protection: Preclinical Large Animal and Clinical Studies - p. 404 43. Chapter 29. Cytidine Deaminase in Myeloprotective Gene Therapy - p. 420 44. Section V: Cancer Therapy Imaging Vectors - p. 435 45. Section V. Cancer Therapy Imaging Vectors - p. 435 46. Chapter 30. Genetically Engineered Salmonella typhimurium for Targeted Cancer Therapy - p. 442 47. Chapter 31. Imaging of Oncolytic Virus Gene Expression - p. 450 48. Chapter 32. Lentiviral-Encoded Sodium Iodide Symporter-Mediated Cancer Gene Therapy - p. 458 49. Chapter 33. Bacteriophage: From Bacteria to a Successful Targeted Systemic Gene Delivery for Cancer - p. 474 50. Section VI: Issues in Trial Design Review and Approval - p. 487 51. Section VI. Issues in Trial Design Review and Approval - p. 487 52. Chapter 34. Issues in Moving Gene Therapy Approaches to Early Clinical Trials - p. 492 53. Chapter 35. The FDA Review Process for Cancer Gene Therapy - p. 500 54. Chapter 36. Ethics in Translational Gene Transfer Research - p. 513 55. Index - p. 525
Gene therapy as a treatment for cancer is at a critical point in its evolution. Exciting new developments in gene targeting and vector technology, coupled with results from the first generation of preclinical and clinical studies have led to the design and testing of new therapeutic approaches. The Third Edition of Gene Therapy of Cancer provides crucial updates on the basic and applied sciences of gene therapy. It offers a comprehensive assessment of the field including the areas of suicide gene therapy, oncogene and suppressor gene targeting, immunotherapy, drug resistance gene therapy, and the genetic modification of stem cells. Researchers at all levels of development, from basic laboratory investigators to clinical practitioners, will find this book to be instructive.
Cancer gene therapy, like cancer therapy in general, is evolving rapidly, testing new concepts, targets and pathways, evoking new technologies, and passing new regulatory hurdles. Its essence, however, has not changed: the hope and challenges of returning altered genes to normal, using targeted gene expression to alter the function of both tumor and microenvironment, and in some cases normal cells, and delivering functionally important genes to specific cell types to increase sensitivity to killing or to protect normal cells from cancer therapies.
In some instances, gene therapy for cancer forms a continuum from gene repair through the use of molecularly modified cells; the use of viral and non-viral vector based gene delivery to both tumor and tumor microenvironment; the use of viral and gene based vaccines; and development of new gene-based therapeutics. The unique mechanistically chosen vector platforms are at the heart of this technology because they allow for direct and selective cell death and transient to sustained delivery of vaccine molecules or molecules that affect the microenvironment, vasculature, or the immune response.
1. Cover image - p. Cover 2. Title page - p. Cover 3. Table of Contents - p. Cover 4. Copyright - p. Cover 5. Dedication - p. IV 6. List of Contributors - p. V 7. Section I: Viral and Nonviral Vector Methodologies: Targets and Approaches - p. V 8. Section I. Viral and Nonviral Vector Methodologies: Targets and Approaches - p. V 9. Chapter 1. Ex Vivo Gene Therapy: Utilization of Genetic Vectors for the Generation of Genetically Modified Cell Products for Therapy - p. 2 10. Chapter 2. Targeting Tumor Vasculature Using Adeno-Associated Virus Phage Vectors Coding Tumor Necrosis Factor-α - p. 12 11. Chapter 3. Viral Insertion Site Detection and Analysis in Cancer Gene Therapy - p. 30 12. Chapter 4. Targeted Systemic Delivery of Therapeutic siRNA - p. 45 13. Chapter 5. Bacterial Delivery of RNAi Effectors - p. 63 14. Chapter 6. Gene-Directed Enzyme Prodrug Cancer Therapy - p. 74 15. Chapter 7. Electroporation Gene Therapy - p. 87 16. Chapter 8. Toxin-Based Cancer Gene Therapy: Under the Control of Oncofetal H19 Regulatory Sequences - p. 103 17. Chapter 9. Gene Therapy in Radiotherapy of Cancer - p. 120 18. Section II: Oncolytic Viruses - p. 129 19. Section II. Oncolytic Viruses - p. 129 20. Chapter 10. Advances in Oncolytic Virotherapy for Brain Tumors - p. 136 21. Chapter 11. Oncolytic Adenoviruses in the Treatment of Cancer in Humans - p. 147 22. Chapter 12. Selectively Replicating Oncolytic Adenoviruses Combined with Chemotherapy, Radiotherapy, or Molecular Targeted Therapy for Treatment of Human Cancers - p. 167 23. Chapter 13. Reoviral Therapy for Cancer: Strategies for Improving Antitumor Efficacy Using Radio- and Chemotherapy - p. 180 24. Chapter 14. Selectively Replicating Herpes Simplex Viral Vectors - p. 196 25. Chapter 15. Modified Oncolytic Herpesviruses for Gene Therapy of Cancer - p. 209 26. Chapter 16. The Lister Strain of Vaccinia Virus as an Anticancer Therapeutic Agent - p. 222 27. Section III: Immunotherapeutics - p. 235 28. Section III. Immunotherapeutics - p. 235 29. Chapter 17. Poxvirus-Based Strategies for Combined Vaccine and Tumor Microenvironment Manipulation - p. 240 30. Chapter 18. Genetically Engineered (T Cell Receptor) T Cells for Adoptive Therapy - p. 254 31. Chapter 19. Genetically Modified Dendritic Cell Vaccines for Solid Tumors - p. 266 32. Chapter 20. Dendritic Cell Vaccination - p. 280 33. Chapter 21. Chemokine Gene-Modified Dendritic Cells for Cancer Therapy - p. 295 34. Chapter 22. The Use of T Cell Costimulation to Enhance the Immunogenicity of Tumors - p. 312 35. Chapter 23. Clinical Application of Plasmid-Based Cancer Vaccines - p. 332 36. Chapter 24. Lentivector Vaccines - p. 341 37. Chapter 25. Therapeutic Efficacy and Systemic Antitumor T Cell Immunity Induced by RheoSwitch-Regulated IL-12 Expression after Intratumoral Injection of Adenovirus Vector or Vector-Transduced Dendritic Cells - p. 357 38. Section IV: Drug Resistance and Metabolism Gene Therapy - p. 373 39. Section IV. Drug Resistance and Metabolism Gene Therapy - p. 373 40. Chapter 26. Clinical Trials Using LV-P140K-MGMT for Gliomas - p. 378 41. Chapter 27. RNA Interference Therapeutics for Tumor Therapy: Promising Work in Progress - p. 387 42. Chapter 28. MGMT Stem Cell Selection and Protection: Preclinical Large Animal and Clinical Studies - p. 404 43. Chapter 29. Cytidine Deaminase in Myeloprotective Gene Therapy - p. 420 44. Section V: Cancer Therapy Imaging Vectors - p. 435 45. Section V. Cancer Therapy Imaging Vectors - p. 435 46. Chapter 30. Genetically Engineered Salmonella typhimurium for Targeted Cancer Therapy - p. 442 47. Chapter 31. Imaging of Oncolytic Virus Gene Expression - p. 450 48. Chapter 32. Lentiviral-Encoded Sodium Iodide Symporter-Mediated Cancer Gene Therapy - p. 458 49. Chapter 33. Bacteriophage: From Bacteria to a Successful Targeted Systemic Gene Delivery for Cancer - p. 474 50. Section VI: Issues in Trial Design Review and Approval - p. 487 51. Section VI. Issues in Trial Design Review and Approval - p. 487 52. Chapter 34. Issues in Moving Gene Therapy Approaches to Early Clinical Trials - p. 492 53. Chapter 35. The FDA Review Process for Cancer Gene Therapy - p. 500 54. Chapter 36. Ethics in Translational Gene Transfer Research - p. 513 55. Index - p. 525
