Viral Therapy of Cancer

by Harrington, Kevin J.; Vile, Richard G.; Pandha, Hardev S.

• ISBN13: 9780470019221
• ISBN10: 0470019220
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-06-09
• Publisher: Wiley

Summary

In the last decade there has been an explosion of interest in viral therapies for cancer. Viral agents have been developed that are harmless to normal tissues but selectively able to kill cancer cells. These agents have been endowed with additional selectivity and potency through genetic manipulation. Increasingly these viruses are undergoing evaluation in clinical trials, both as single agents and in combination with standard chemotherapy and radiotherapy. 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 researchViral Therapy of Cancer is essential reading for both basic scientists and clinicians with an interest in viral therapy and gene therapy.

Author Biography

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.

Table of Contents

Foreword

Preface

Contributors

Adenoviruses

Introduction

Viral structure and life cycle

Adenoviral vectors

Targeting adenoviral vectors

Clinical applications of adenoviral gene therapy

Adenoviral vectors for immunotherapy

Adenoviral vectors for suicide gene therapy

Adenoviral vectors for gene replacement therapy

Oncolytic adenoviral therapy

Adverse outcomes of adenoviral gene therapy

Summary

References

Application of HSV-1 Vectors to the treatment of cancer

Introduction

Basic biology of HSV

Replication competent or oncolytic vectors

Replication defective vectors

Amplicons

Impediments to the efficacy of HSV vectors for cancer gene therapy

Strategies to enhance the efficacy and specificity of HSV vectors for cancer gene therapy

Summary and conclusions

Acknowledgements

References

Adeno-associated virus

Introduction

Biology and life cycle of AAV

AAV serotypes

Production of recombinant AAV

Gene therapy for cancer treatment

Anti-oncogenic properties of AAV

Molecular chemotherapy studies with rAAV

AAV-mediated sustained transgene expression as a potential cancer gene therapy strategy

rAAV vectors have advantages in stimulating T helper 1/cytotoxic T lymphocyte responses

rAAV vectors can be used to initiate immune responses

Altering AAV tropism for tumour-specific delivery

Clinical trials involving rAAV

Conclusion

Acknowledgements

References

Retroviruses

Introduction

Structure of retroviral particles

Retroviral genome

Retroviral life cycle

Retroviral vectors

Safety of retroviral vectors: insertional mutagenesis

Gene therapy of X-linked SCID

Retroviral cancer gene therapy

Immunomodulatory approaches

Conclusions

References

Lentiviral vectors for cancer gene therapy

Development of Lentiviral vectors (LV)

Targeting of transgene expression

Host immune responses to LV and their transgene

Transgenesis

Haematopoietic stem cell gene transfer

Cancer treatment by LV

Approved clinical trials using LV

Conclusions

References

Poxviruses as immunomodulatory cancer therapeutics

Introduction

General features of poxvirus structure and biology

Clinically applicable poxviruses

Poxviruses as potential cancer therapeutics

Clinical experience with poxviruses

Conclusion

References

Oncolytic herpes simplex viruses

Introduction

Herpes simplex virology

Properties of HSV relevant to oncolytic virus therapy

Mutations giving tumour-selective replication

Oncolytic HSV expressing fusogenic membrane glycoproteins (FMG)

Prodrug activation therapy and oncolytic HSV

Combination of oncolytic HSV with immunomodulatory gene expression

Combination of conventional therapies with oncolytic HSV

Summary

Acknowledgement

References

Selective tumour cell cytoto

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