Second Generation Cell and Gene-Based Therapies: Biological Advances, Clinical Outcomes, and Strategies for Capitalisation serves as the only volume to the market to bridge basic science, clinical therapy, technology development, and business in the field of cellular therapy/cytotherapy. After more than two decades of painstaking fundamental research, the concept of therapeutic cells (stem cells, genes, etc.), beyond the concept of vaccines, is reaching clinical trial, with mounting confidence in the safety and efficacy of these products. Nonetheless, numerous incremental technical advances remain to be achieved. Thus, this volume highlights the possible R&D paths, which will ultimately facilitate clinical delivery of cutting edge curative products.
The next waves of innovation are reviewed in depth for hematopoietic stem cells, mesenchymal stem cells, tissue engineering, CAR-T cells, and cells of the immune system, as well as for enabling technologies such as gene and genome editing. Additionally, deep dives in product fundamentals, history of science, pathobiology of diseases, scientific and technological bases, and financing and technology adoption constraints are taken to unravel what will shape the cytotherapy industry to the horizon 2025 and beyond. The outcome is not simply a scientific book, but a global perspective on the nascent field combining science, business, and strategic fundamentals.
1. Introduction - p. 91 2. Natural Killer Cells and Cancer - p. 94 3. Natural Killer Cell–Based Immunotherapy - p. 102 4. Combination Therapy With Natural Killer Cell–Based Immune Therapy - p. 114 5. Ongoing Clinical Trials - p. 123 6. Clinical Development Status of Chimeric Antigen Receptor Natural Killer Cells - p. 136 7. Perspectives - p. 140 8. Chapter 6. Pluripotent Stem Cell–Derived Islet Replacement Therapy for Diabetes - p. 157 9. Chapter 7. Harnessing in Silico Technologies to Develop and Augment Second-Generation Cell-Based Therapies - p. 183 10. Chapter 8. Second Generation Genome Editing Technologies in Drug Discovery - p. 213 11. Chapter 9. The Next Wave: Tissue Replacement and Organ Replacement - p. 243 12. Chapter 10. Combining Stem Cells and Materials for Nerve Tissue Regeneration - p. 269 13. Part 2. Translation - p. 281 14. Chapter 11. Gene Therapy Clinical Trials: Past, Present and Future - p. 285 15. Chapter 12. CAR-T Cell Clinical Trials Experience – Past, Present and Future - p. 303 16. History of CAR-T Cell Therapy Clinical Trials - p. 303 17. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Chronic Lymphocytic Leukaemias - p. 306 18. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Adult Acute Lymphoblastic Leukaemia - p. 309 19. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Paediatric Acute Lymphoblastic Leukaemia - p. 315 20. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Non-Hodgkin’s Lymphoma - p. 321 21. CAR-T Cell Therapies Targeting Antigens Other Than CD19 for Haematological Malignancies - p. 326 22. CAR-T cells in Solid Tumours - p. 329 23. Challenges With CAR-T CELL Therapies - p. 333 24. Biomarkers - p. 340 25. Academia-Industry Partnerships - p. 344 26. Research in China - p. 347 27. Regulatory Challenges and Solutions - p. 357 28. Commercial, Value and Access Challenges for the Successful Adoption of CAR-T CELL Therapies - p. 359 29. Perspectives - p. 362 30. Chapter 13. T Cell Receptor Engineered T Cell Therapy in Oncology - p. 377 31. Chapter 14. Cytotherapy Clinical Trials in Genetic Disorders of the Blood and Options for Reimbursement - p. 409 32. Part 3. The Next Frontier - p. 432 33. Chapter 15. Mesenchymal Stromal Cell Therapies – The Next Frontiers - p. 435 34. Chapter 16. Regenerative Medicine and Ageing: Is Senescence Reprogrammable? - p. 449 35. Chapter 17. Deciphering the Systems Architecture of the Brain Using Molecular Can Openers - p. 461 36. Chapter 18. Harnessing the Therapeutic Potential of Dendritic Cells - p. 489 37. Chapter 19. Brief Overview of Chimeric Antigen Receptor–Mediated Immunotherapy for Glioblastoma Multiforme - p. 507 38. Chapter 20. Combination Therapies in Solid Tumour Oncology - p. 515 39. Part 4. Perspectives - p. 578 40. Chapter 21. Gene-Editing Technologies in Adoptive T Cell Therapy for Cancer: An Ethical Analysis - p. 581 41. Chapter 22. Decisions in the Development Lifecycle of Cell and Gene Therapies - p. 597 42. Chapter 23. CAR-T: From Concepts to Products – Now What? - p. 633 43. Chapter 24. Strategic Alliances in Cytotherapies and Gene Therapies: Funding the New Wave of Cell Therapeutics - p. 649 44. Chapter 25. The Role of Governments in the Commercial Emergence of Radical Innovation: The Case of the United Kingdom - p. 659 45. Chapter 26. Patenting Trends in Chimeric Antigen Receptor Technologies - p. 689 46. Chapter 27. Reimbursement and Payment Models for Therapies With Transformative and Curative Intent - p. 705 47. Chapter 28. Commercialising CAR-T Therapies: The Evolution of a Revolution - p. 747 48. Chapter 29. Will You Move The Needle of Medicine? - p. 777 49. Index - p. 783
Second Generation Cell and Gene-Based Therapies: Biological Advances, Clinical Outcomes, and Strategies for Capitalisation serves as the only volume to the market to bridge basic science, clinical therapy, technology development, and business in the field of cellular therapy/cytotherapy. After more than two decades of painstaking fundamental research, the concept of therapeutic cells (stem cells, genes, etc.), beyond the concept of vaccines, is reaching clinical trial, with mounting confidence in the safety and efficacy of these products. Nonetheless, numerous incremental technical advances remain to be achieved. Thus, this volume highlights the possible R&D paths, which will ultimately facilitate clinical delivery of cutting edge curative products.
The next waves of innovation are reviewed in depth for hematopoietic stem cells, mesenchymal stem cells, tissue engineering, CAR-T cells, and cells of the immune system, as well as for enabling technologies such as gene and genome editing. Additionally, deep dives in product fundamentals, history of science, pathobiology of diseases, scientific and technological bases, and financing and technology adoption constraints are taken to unravel what will shape the cytotherapy industry to the horizon 2025 and beyond. The outcome is not simply a scientific book, but a global perspective on the nascent field combining science, business, and strategic fundamentals.
1. Introduction - p. 91 2. Natural Killer Cells and Cancer - p. 94 3. Natural Killer Cell–Based Immunotherapy - p. 102 4. Combination Therapy With Natural Killer Cell–Based Immune Therapy - p. 114 5. Ongoing Clinical Trials - p. 123 6. Clinical Development Status of Chimeric Antigen Receptor Natural Killer Cells - p. 136 7. Perspectives - p. 140 8. Chapter 6. Pluripotent Stem Cell–Derived Islet Replacement Therapy for Diabetes - p. 157 9. Chapter 7. Harnessing in Silico Technologies to Develop and Augment Second-Generation Cell-Based Therapies - p. 183 10. Chapter 8. Second Generation Genome Editing Technologies in Drug Discovery - p. 213 11. Chapter 9. The Next Wave: Tissue Replacement and Organ Replacement - p. 243 12. Chapter 10. Combining Stem Cells and Materials for Nerve Tissue Regeneration - p. 269 13. Part 2. Translation - p. 281 14. Chapter 11. Gene Therapy Clinical Trials: Past, Present and Future - p. 285 15. Chapter 12. CAR-T Cell Clinical Trials Experience – Past, Present and Future - p. 303 16. History of CAR-T Cell Therapy Clinical Trials - p. 303 17. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Chronic Lymphocytic Leukaemias - p. 306 18. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Adult Acute Lymphoblastic Leukaemia - p. 309 19. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Paediatric Acute Lymphoblastic Leukaemia - p. 315 20. Clinical Outcome of CD19-Targeted CAR-T cells in B-Cell Haematological Malignancies: Non-Hodgkin’s Lymphoma - p. 321 21. CAR-T Cell Therapies Targeting Antigens Other Than CD19 for Haematological Malignancies - p. 326 22. CAR-T cells in Solid Tumours - p. 329 23. Challenges With CAR-T CELL Therapies - p. 333 24. Biomarkers - p. 340 25. Academia-Industry Partnerships - p. 344 26. Research in China - p. 347 27. Regulatory Challenges and Solutions - p. 357 28. Commercial, Value and Access Challenges for the Successful Adoption of CAR-T CELL Therapies - p. 359 29. Perspectives - p. 362 30. Chapter 13. T Cell Receptor Engineered T Cell Therapy in Oncology - p. 377 31. Chapter 14. Cytotherapy Clinical Trials in Genetic Disorders of the Blood and Options for Reimbursement - p. 409 32. Part 3. The Next Frontier - p. 432 33. Chapter 15. Mesenchymal Stromal Cell Therapies – The Next Frontiers - p. 435 34. Chapter 16. Regenerative Medicine and Ageing: Is Senescence Reprogrammable? - p. 449 35. Chapter 17. Deciphering the Systems Architecture of the Brain Using Molecular Can Openers - p. 461 36. Chapter 18. Harnessing the Therapeutic Potential of Dendritic Cells - p. 489 37. Chapter 19. Brief Overview of Chimeric Antigen Receptor–Mediated Immunotherapy for Glioblastoma Multiforme - p. 507 38. Chapter 20. Combination Therapies in Solid Tumour Oncology - p. 515 39. Part 4. Perspectives - p. 578 40. Chapter 21. Gene-Editing Technologies in Adoptive T Cell Therapy for Cancer: An Ethical Analysis - p. 581 41. Chapter 22. Decisions in the Development Lifecycle of Cell and Gene Therapies - p. 597 42. Chapter 23. CAR-T: From Concepts to Products – Now What? - p. 633 43. Chapter 24. Strategic Alliances in Cytotherapies and Gene Therapies: Funding the New Wave of Cell Therapeutics - p. 649 44. Chapter 25. The Role of Governments in the Commercial Emergence of Radical Innovation: The Case of the United Kingdom - p. 659 45. Chapter 26. Patenting Trends in Chimeric Antigen Receptor Technologies - p. 689 46. Chapter 27. Reimbursement and Payment Models for Therapies With Transformative and Curative Intent - p. 705 47. Chapter 28. Commercialising CAR-T Therapies: The Evolution of a Revolution - p. 747 48. Chapter 29. Will You Move The Needle of Medicine? - p. 777 49. Index - p. 783
