GENE THERAPY FOR CANCER
Transforming Growth Factor-G in Cancer Therapy, Volume II: Cancer Treatment and Therapy, edited by Sonia Jakowlew, 2007
Transforming Growth Factor-G in Cancer Therapy, Volume 1: Basic and Clinical Biology, edited by Sonia Jakowlew, 2007 Microtubule Targets in Cancer Therapy,
edited by Antonio T. Fojo, 2007 Cytokines in the Genesis and Treatment of
Cancer, edited by Michael A. Caligiuri, Michael T. Lotze, and Frances R. Balkwill, 2007
Regional Cancer Therapy, edited by Peter M.
Schlag and Ulrike Stein, 2007
Gene Therapy for Cancer, edited by Kelly K.
Hunt, Stephan A. Vorburger, and Stephen G. Swisher, 2007
Deoxynucleoside Analogs in Cancer Therapy, edited by Godefridus J. Peters, 2006 Cancer Drug Resistance, edited by Beverly A.
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Histone Deacetylases: Transcriptional Regula- tion and Other Cellular Functions, edited by Eric Verdin, 2006
Immunotherapy of Cancer, edited by Mary L. Disis, 2006
Biomarkers in Breast Cancer: Molecular Diagnostics for Predicting and Monitoring Therapeutic Effect, edited by Giampietro Gasparini and Daniel F. Hayes, 2006 Protein Tyrosine Kinases: From Inhibitors to
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Bone Metastasis: Experimental and Clinical Therapeutics, edited by Gurmit Singh and Shafaat A. Rabbani, 2005
The Oncogenomics Handbook, edited by William J. LaRochelle and Richard A.
Shimkets, 2005
Camptothecins in Cancer Therapy, edited by Thomas G. Burke and Val R. Adams, 2005
CANCER DRUG DISCOVERY AND DEVELOPMENT
BEVERLY A. TEICHER, SERIES EDITOR
Combination Cancer Therapy: Modulators and Potentiators, edited by Gary K.
Schwartz, 2005
Cancer Chemoprevention, Volume 2: Strategies for Cancer Chemoprevention, edited by Gary J. Kelloff, Ernest T. Hawk, and Caroline C.
Sigman, 2005
Death Receptors in Cancer Therapy, edited by Wafik S. El-Deiry, 2005
Cancer Chemoprevention, Volume 1: Promising Cancer Chemopreventive Agents, edited by Gary J. Kelloff, Ernest T. Hawk, and Caroline C. Sigman, 2004
Proteasome Inhibitors in Cancer Therapy, edited by Julian Adams, 2004
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DNA Repair in Cancer Therapy, edited by Lawrence C. Panasci and Moulay A. Alaoui- Jamali, 2004
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and Pharmacodynamics, edited by William D. Figg and Howard L. McLeod, 2004 Anticancer Drug Development Guide: Preclinical
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Handbook of Cancer Vaccines, edited by Michael A. Morse, Timothy M. Clay, and Kim H. Lyerly, 2004
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GENE THERAPY FOR CANCER
Edited by
KELLY K. HUNT, MD
The University of Texas M. D. Anderson Cancer Center, Houston, TX
STEPHAN A. VORBURGER, MD, MCR
Inselspital Bern, University of Bern, Bern, Switzerland
STEPHEN G. SWISHER, MD
The University of Texas M. D. Anderson Cancer Center, Houston, TX
© 2007 Humana Press Inc.
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Gene therapy for cancer / edited by Kelly K. Hunt, Stephan A. Vorburger, Stephen G. Swisher.
p. ; cm. — (Cancer drug discovery and development) Includes bibliographical references and index.
ISBN 1-58829-472-2 (alk. paper)
1. Cancer—Gene therapy. I. Hunt, Kelly K. II. Vorburger, Stephan A. III. Swisher, Stephen G. IV. Series.
[DNLM: 1. Neoplasms—genetics. 2. Neoplasms—therapy. 3. Gene Therapy—methods. QZ 266 G3253 2007]
RC271.G45G463 2007
616.99’40694—dc22 2006012653
v
PREFACE
The possibility of treating cancer, a disease defined by genetic defects, by introducing genes targeting these very alterations has led to an immense interest in gene therapy for cancer. Although incremental successes have been realized, enthusiasm for gene therapy has declined due to an increasing number of obstacles. These obstacles include vector systems that do not reach systemic metastases, therapeutic genes with redundant mecha- nisms allowing for cellular resistance, and toxicities in clinical trials leading to premature closure of these studies. Different tactics to overcome or circumvent these obstacles have catalyzed the development of a wide range of gene therapy approaches. Thus far, almost two-thirds of gene therapy trials have focused on cancer. This reflects the concept that gene therapy approaches for the treatment of cancer do not necessarily require long-term expression of the gene as is necessary for the treatment of primary genetic defects like hemophilia or juvenile diabetes. Unlike the treatment of genetic defects, where expres- sion of the corrected gene needs to be strong, permanent and, sometimes regulated, tactics to treat tumors can be based on temporary and locally limited effects. In addition, cancer cells have different properties than normal cells and this allows for targeting gene therapy to specific cells, a major advantage over current antitumor therapies, which are also toxic to normal cells and tissues.
Gene Therapy for Cancer covers the current ideas and technology of gene therapy, as well as the demanding task of bringing it to and applying it in clinical trials. The book is divided into three major parts: (1) Vectors used in gene therapy against cancer, (2) targets and specific approaches for the therapy of cancer, and (3) clinical applications of cancer gene therapy.
The delivery of an antitumor gene, a toxic agent, or an immunostimulating drug selectively to tumor cells is one of the most crucial steps in achieving successful cancer gene therapy. We have dedicated a considerable portion of Gene Therapy for Cancer to a description of the various aspects of gene delivery including vehicles (vectors), their characteristics, and production methods.
Knowledge of the specific strategies and targets for the treatment of cancer has increased dramatically over the past decade. These range from methods that induce immediate cancer cell death through expression of genes that trigger the cell-death program or by reactivating pathways that render mutated cells susceptible to antitumor agents. Additional methods run the gamut from the correction of underlying defects at molecular levels to activation of the immune system or the tumor microenvironment. Understanding the basic underlying oncogenic changes allows for development of vectors engineered to exploit these gene mutations through selective spread of the vector in tumor cells with the specific changes.
Background knowledge, technical details, and preclinical and clinical results are pro- vided by specialists in each of these approaches.
Probably more so than in any other antitumor therapy, bringing gene therapy approaches to the clinic is a difficult task burdened by numerous regulations and limited by scarce funding opportunities. We have asked experts in clinical gene therapy trials to discuss the
vi Preface
trials and tribulations of realizing advances in gene therapy at the preclinical level to the benefit of patients with cancer. The readers will gain significant insight into these difficulties and learn how to overcome the obstacles on the way from the laboratory to the bedside. Gene therapy approaches and results that have reached the stage of clinical testing are described by their principal investigators.
With Gene Therapy for Cancer we have sought to provide a comprehensive and in- depth view of currently available techniques for cancer gene therapy, including their limitations and the potential for future advances. This should prove to be a valuable resource for both researchers and clinicians in the field. With this approach we hope to provide an oppor- tunity for clinicians and researchers to communicate their perspectives, allowing for increased collaboration and perhaps more rapid advances in this challenging field.
We would like to thank all the specialists who dedicated their valuable time to provide the most important and exciting advances in cancer gene therapy for this book. We are deeply grateful to our families for their continuous support, endless patience, and under- standing.
Kelly K. Hunt, MD Stephan A. Vorburger, MD Stephen G. Swisher, MD
Preface ... v Contributors ... ix
I VECTORS
1 Adenovector-Mediated Cancer Gene Therapy ... 3 Bingliang Fang and Jack A. Roth
2 Efficacy, Toxicity, and Immunogenicity of Adenoviral Vectors ... 23 Dmitry M. Shayakhmetov
3 Lentiviral and Retroviral Vector Systems ... 39 Renata Stripecke and Noriyuki Kasahara
4 Vaccinia and Pox-Virus ... 73 Sricharan Chalikonda and David L. Bartlett
5 Herpes Simplex Virus as a Therapy for Cancer ... 87 Ian J. Mohr
6 Alphavirus Vectors for Gene Therapy Applications ... 109 Kenneth Lundstrom
7 Vesicular Stomatitis Virus and RNA Viruses
as Gene Therapy Vectors ... 121 Glen N. Barber
8 Parvovirus Vectors ... 141 Selvarangan Ponnazhagan
9 Nonviral Vector Systems ... 157 Pui-yan Lee and Leaf Huang
II GENE THERAPY APPROACHES
10 Oncogenes, Tumor Suppressor Genes, and Apoptosis-Inducing
Genes Utilized in Cancer Gene Therapy ... 173 Lidong Zhang and Bingliang Fang
11 Gene Silencing Therapy Against Cancer ... 185 Chao-Zhong Song
12 Tumor Targeting–Retargeted Adenovirus ... 197 Masato Yamamoto and David T. Curiel
13 Oncolytic Herpes Simplex for Gene Therapy
in Preclinical and Clinical Trials ... 213 Richard H. Pin, Maura Reinblatt, Yuman Fong,
and William R. Jarnagin
vii
CONTENTS
14 Cytokine Gene Therapy for Genitourinary Cancer ... 223 Terry L. Timme, Tetsuo Fujita, Hongyu Wang, Koji Naruishi, Dov Kadmon, Robert J. Amato, Brian J. Miles, Gustavo Ayala, Thomas M. Wheeler, Bin S. Teh, E. Brian Butler,
and Timothy C. Thompson
15 Combination of Gene Therapy with Radiation ... 243 Anupama Munshi and Raymond E. Meyn
16 Gene Transfer for Chemoprotection and Enrichment
of Hematopoietic Stem Cells ... 257 Justin C. Roth and Stanton L. Gerson
17 Nonviral Genetic Vaccines for Cancer ... 281 Steven R. Little, Daniel G. Anderson, and Robert Langer
18 Gene Therapy Targeted at Angiogenesis and Lymphangiogenesis for Cancer Treatment ... 301 Anita T. Tandle and Steven K. Libutti
19 Tumor-Specific Replicating Adenoviruses:
) 24 for Human Gliomas ... 331 Giacomo G. Vecil, Juan Fueyo, and Frederick F. Lang
III CLINICAL APPLICATIONS
20 Problems, Side Effects, and Disappointments
in Clinical Cancer Gene Therapy ... 351 Ta-Chiang Liu and David H. Kirn
21 Trials and Tribulations in Developing Clinical Trials
of Gene Therapy: E1A for Breast or Ovarian Cancer ... 387 Naoto T. Ueno, Judith K. Wolf, David M. Gershenson,
Gabriel N. Hortobagyi, and Mien-Chie Hung
22 Phase I Clinical Experience with Intravenous Administration
of PV701, an Oncolytic Virus ... 399 Andrew L. Pecora and Robert M. Lorence
23 MDA-7/IL-24 as a Multi-Modality Therapy for Cancer ... 413 Sunil Chada, Dora Bocangel, Abujiang Pataer,
Abner M. Mhashilkar, Satoshi Inoue, Ryo Miyahara, Jack A. Roth, Elizabeth A. Grimm, Stephen G. Swisher, Kelly K. Hunt, and Rajagopal Ramesh
24 Development of Therapeutic Genes for Breast Cancer Treatment .... 435 Mien-Chie Hung and Duen-Hwa Yan
25 Steps in a Translational Cancer Gene Therapy Trial ... 447 Urs W. von Holzen and Stephen G. Swisher
Index ... 461
viii Contents
ROBERT J. AMATO • Scott Department of Urology, Baylor College of Medicine, Houston, TX DANIEL G. ANDERSON • Chemical Engineering Department, Massachusetts Institute of
Technology, Cambridge, MA
GUSTAVO AYALA • Department of Pathology, Baylor College of Medicine, Houston, TX GLEN N. BARBER • Department of Microbiology and Immunology, University of Miami
School of Medicine, Miami, FL
DAVID L. BARTLETT • Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA DORA BOCANGEL • Introgen Therapeutics, Houston, TX
E. BRIAN BUTLER • Department of Radiology, Baylor College of Medicine, Houston, TX SUNIL CHADA • Introgen Therapeutics, Houston, TX
SRICHARAN CHALIKONDA • Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA
DAVID T. CURIEL • Gene Therapy Center, University of Alabama, Birmingham, AL BINGLIANG FANG • Department of Thoracic and Cardiovascular Surgery–Research,
The University of Texas M.D. Anderson Cancer Center, Houston, TX
YUMAN FONG • Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
JUAN FUEYO • Department of Neuro-Oncology/Research, The University of Texas M. D.
Anderson Cancer Center, Houston, TX
TETSUO FUJITA • Scott Department of Urology, Baylor College of Medicine, Houston, TX DAVID M. GERSHENSON • Department of Gynecologic Oncology, The University of
Texas M.D. Anderson Cancer Center, Houston, TX
STANTON L. GERSON • Division of Hematology-Oncology, Case Western Reserve University School of Medicine, Cleveland, OH
ELIZABETH A. GRIMM • Department of Experimental Therapuetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
GABRIEL N. HORTOBAGYI • Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
LEAF HUANG • Center for Pharmacogenetics, Department of Pharmaceutical Science, University of Pittsburgh, Pittsburgh, PA
MIEN-CHIE HUNG • Department of Molecular & Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
KELLY K. HUNT • Department of Surgical Oncology, The University of Texas M.D.
Anderson Cancer Center, Houston, TX
CONTRIBUTORS
ix
SATOSHI INOUE • Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX
WILLIAM R. JARNAGIN • Hepatobiliary Service, Department of Surgery, Memorial Sloan- Kettering Cancer Center, New York, NY
DOV KADMON • Scott Department of Urology, Baylor College of Medicine, Houston, TX NORIYUKI KASAHARA • Department of Medicine, UCLA Geffen School of Medicine,
Macdonald Research Laboratories, Los Angeles, CA
DAVID H. KIRN • Department of Clinical Pharmacology, University of Oxford Medical School, Oxford, UK
FREDERICK F. LANG • Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX
ROBERT S. LANGER • Chemical & Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA
PUI-YAN LEE • Center for Pharmacogenetics, Department of Pharmaceutical Science, University of Pittsburgh, Pittsburgh, PA
STEVEN K. LIBUTTI • Surgery Branch, National Cancer Institute, Bethesda, MD
STEVEN R. LITTLE • Departments of Chemical Engineering and Bioengineering, University of Pittsburgh, Pittsburgh, PA
TA-CHIANG LIU • Molecular Neurosurgery Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA
ROBERT M. LORENCE • Wellstat Biologics Corporation, Gaithersburg, MD KENNETH LUNDSTROM • BioXtal / Cancer Therapeutic Sciences, Switzerland
RAYMOND E. MEYN, JR. • Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
ABNER M. MHASHILKAR • Introgen Therapeutics, Houston, TX
BRIAN J. MILES • Scott Department of Urology, Baylor College of Medicine, Houston, TX RIO MIYAHARA • Department of Thoracic and Cardiovascular Surgery, The University
of Texas M. D. Anderson Cancer Center, Houston, TX
IAN J. MOHR • Department of Microbiology, New York University School of Medicine, New York, NY
ANUPAMA MUNSHI • Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
KOJI NARUISHI • Scott Department of Urology, Baylor College of Medicine, Houston, TX ABUJIANG PATAER • Department of Thoracic and Cardiovascular Surgery, The University
of Texas M.D. Anderson Cancer Center, Houston, TX
ANDREW L. PECORA • The Cancer Center, Hackensack University Medical Center, Hackensack, NJ
RICHARD H. PIN • Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
SELVARANGAN PONNAZHAGAN • Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
x Contributors
RAJAGOPAL RAMESH • Department of Thoracic and Cardiovascular Surgery–Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX
MAURA REINBLATT • Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
JACK A. ROTH • Department of Thoracic and Cardiovascular Surgery–Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX
JUSTIN C. ROTH • Division of Hematology/Oncology, Case Western Reserve University, Cleveland, OH
DMITRY M. SHAYAKHMETOV • Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA
CHAO-ZHONG SONG • Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA
RENATA STRIPECKE • Department of Medicine, David Geffen School of Medicine, University of California (UCLA), Los Angeles, CA
STEPHEN G. SWISHER • Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX
ANITA T. TANDLE • Surgery Branch, National Cancer Institute, Bethesda, MD BIN S. TEH • Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX TIMOTHY C. THOMPSON • Scott Department of Urology, Baylor College of Medicine,
Houston, TX
TERRY L. TIMME • Scott Department of Urology, Baylor College of Medicine, Houston, TX NAOTO T. UENO • Department of Blood and Marrow Transplantation, The University
of Texas M. D. Anderson Cancer Center, Houston, TX
GIACOMO G. VECIL • Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX
URS VON HOLZEN • Department of Surgical Oncology, The University of Texas M. D.
Anderson Cancer Center, Houston, TX
STEPHAN A. VORBURGER • Department of Visceral and Transplantation Surgery, Inselspital Bern, University of Bern, Bern, Switzerland
HONGYU WANG • Scott Department of Urology, Baylor College of Medicine, Houston, TX THOMAS M. WHEELER • Department of Pathology, Baylor College of Medicine, Houston, TX JUDITH K. WOLF • Department of Gynecologic Oncology, The University of Texas M.
D. Anderson Cancer Center, Houston, TX
MASATO YAMAMOTO • Gene Therapy Center, University of Alabama, Birmingham, AL DUEN-HWA YAN • Department of Molecular and Cellular Oncology, The University of
Texas M. D. Anderson Cancer Center, Houston, TX
LIDONG ZHANG • Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX
Contributors xi
