Gene Therapy for Cancer

by Hunt, Kelly K., M.D.; Vorburger, Stephen A., M.D.; Swisher, Stephen G., M.D.

• ISBN13: 9781588294722
• ISBN10: 1588294722
• Edition: 1st
• Format: Hardcover
• Copyright: 2007-02-03
• Publisher: Humana Pr Inc

Summary

The possibility of treating cancer, a disease frequently defined by genetic defects, by introducing genes that target these very alterations has generated tremendous enthusiasm. This enthusiasm, however, has been tempered by an increasing number of obstacles to successful therapy, including vector systems that do not reach systemic metastases, therapeutic genes with redundant mechanisms allowing for cellular resistance, and toxicities in clinical trials that result in premature closure. The three comprehensive sections of this volume present currently available cancer gene therapy techniques, with specific attention to these trouble spots. Part I describes the various aspects of gene delivery including vehicles, or vectors, and their respective characteristics and production methods. In Part II, the contributors discuss strategies and targets for the treatment of cancer, including methods for cell-death therapies, correction of underlying genetic defects at the molecular level, and activation of the immune system or tumor microenvironment. The contributors provide a succinct framework for understanding the basic underlying oncogenic changes, which encourages the development of vectors engineered to exploit these gene mutations through selective spread of the vector in tumor cells with the specific changes. Finally, in Part III, experts in clinical gene therapy trials discuss the difficulties inherent in bringing gene therapy treatment for cancer to the clinic, and principal investigators present gene therapy approaches in the clinical testing stage and the results that have reached the stage of clinical testing.of these trials.

Table of Contents

Preface	p. v
Contributors	p. ix
Vectors
Adenovector-Mediated Cancer Gene Therapy	p. 3
Efficacy, Toxicity, and Immunogenicity of Adenoviral Vectors	p. 23
Lentiviral and Retroviral Vector Systems	p. 39
Vaccinia and Pox-Virus	p. 73
Herpes Simplex Virus as a Therapy for Cancer	p. 87
Alphavirus Vectors for Gene Therapy Applications	p. 109
Vesicular Stomatitis Virus and RNA Viruses as Gene Therapy Vectors	p. 121
Parvovirus Vectors	p. 141
Nonviral Vector Systems	p. 157
Gene Therapy Approaches
Oncogenes, Tumor Suppressor Genes, and Apoptosis-Inducing Genes Utilized in Cancer Gene Therapy	p. 173
Gene Silencing Therapy Against Cancer	p. 185
Tumor Targeting-Retargeted Adenovirus	p. 197
Oncolytic Herpes Simplex for Gene Therapy in Preclinical and Clinical Trials	p. 213
Cytokine Gene Therapy for Genitourinary Cancer	p. 223
Combination of Gene Therapy with Radiation	p. 243
Gene Transfer for Chemoprotection and Enrichment of Hematopoietic Stem Cells	p. 257
Nonviral Genetic Vaccines for Cancer	p. 281
Gene Therapy Targeted at Angiogenesis and Lymphangiogenesis for Cancer Treatment	p. 301
Tumor-Specific Replicating Adenoviruses: [Delta] 24 for Human Gliomas	p. 331
Clinical Applications
Problems, Side Effects, and Disappointments in Clinical Cancer Gene Therapy	p. 351
Trials and Tribulations in Developing Clinical Trials of Gene Therapy: E1A for Breast or Ovarian Cancer	p. 387
Phase I Clinical Experience with Intravenous Administration of PV701, an Oncolytic Virus	p. 399
MDA-7/IL-24 as a Multi-Modality Therapy for Cancer	p. 413
Development of Therapeutic Genes for Breast Cancer Treatment	p. 435
Steps in a Translational Cancer Gene Therapy Trial	p. 447
Index	p. 461
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