Cellular therapy of cancer: development of gene therapy based approaches / ed.: R.E.Hawkins. - Singapore [et al.]: World scientific, 2014. - vii, 201 p.: ill., tab. - Bibliogr. at the end of the chapters. - ISBN 978-981-4295-13-0  Место хранения:   02 | Отделение ГПНТБ СО РАН | Новосибирск

Оглавление / Contents

Chapter 1. Challenges of T-Cell Therapy ......................... 1 Naomi Taylor, Anna Mondino and Balbino Alarcon 1.1 T-Cell Homeostasis ......................................... 1 1.2 Lymphopenia and Immune Responsiveness to Self-Antigens ..... 2 1.3 CD4 and CD8 T-Cell Differentiation States .................. 3 1.4 T-Cell Persistence and Trafficking to Tumor ................ 6 1.5 Choice of Target Antigen ................................... 9 References ...................................................... 9 Chapter 2. Gene Transfer into T Cells .......................... 19 David Gilham and Hinrich Abken 2.1 Introduction .............................................. 19 2.2 γ-Retroviral Vectors to Generate Gene-Modified T Cells .... 21 2.3 The Potential Drawbacks of γ-Retroviral Vectors, for T-Cell Gene Therapy ....................................... 22 2.4 Improving All Aspects of γ-Retroviral Gene Transfer to Preserve or Enhance Antigen-Specific T-Cell Function In Vivo ................................................... 26 2.5 Lentiviral Vectors to Transduce Minimally Stimulated and Quiescent Primary Human T Cells ........................... 29 2.6 Other Viral Vectors Used to Transduce Primary Human T Cells ................................................... 31 2.7 Non-Viral Gene Transfer Into Primary Human T Cells: Plasmid-Based Systems ..................................... 33 2.8 Non-Viral Gene Transfer Into Primary Human T Cells: Transposon Technology ..................................... 34 2.9 Non-Viral Gene Transfer Into Primary Human T Cells: RNA Vectors ................................................... 35 2.10 Mouse Models of Gene-Modified T-Cell Therapy .............. 38 2.11 Summary ................................................... 38 References ..................................................... 39 Chapter 3. TCR-Engineered T cells .............................. 49 Reno Debets and Ton Schumacher 3.1 Introduction .............................................. 49 3.2 Generation of TCR T Cells That are Not or Minimally Self-Reactive ............................................. 52 3.3 Generation of TCR T Cells with Enhanced Functional Avidity ................................................... 60 3.4 Next Steps in TCR Gene Therapy ............................ 67 References ..................................................... 70 Chapter 4. T-Bodies: Antibody-Based Engineered T-Cell Receptors ...................................................... 83 John Bridgeman, Andreas A. Hombach, David Gilham, Zelig Eshhar and Hinrich Abken 4.1 Overview .................................................. 83 4.2 A Long Way to the One-Chain Format: A Brief History of T-Bodies .................................................. 84 4.3 From Structure to Function ................................ 85 4.4 Clinical Studies ......................................... 103 4.5 Perspectives ............................................. 111 4.6 Summary .................................................. 116 References .................................................... 117 Chapter 5 T-Cell Engineering and Expansion - GMP Issues ..... 131 Cor Lamers and Ryan Guest 5.1 Introduction ............................................. 131 5.2 Clinical Vectors ......................................... 133 5.3 Ex Vivo Generation of Gene-Modified T Cells .............. 144 5.4 Data Management and Regulatory Aspects ................... 163 5.5 Future Developments ...................................... 165 References .................................................... 167 Chapter 6. Clinical Trial Design .............................. 179 Robert Hawkins, John Haanen and Fiona Thistlethwaite 6.1 Introduction ............................................. 179 6.2 Background ............................................... 179 6.3 TIL Therapy .............................................. 181 6.4 Engineered T Cells - Clinical Trials ..................... 186 6.5 Toxicities and Safety of ACT ............................. 190 6.6 Future Strategies ........................................ 193 6.7 Conclusions .............................................. 196 References .................................................... 196