Gene Therapy of Cancer

by Lattime; Gerson; Gerson

• ISBN13: 9780124375512
• ISBN10: 0124375510
• Edition: 2nd
• Format: Hardcover
• Copyright: 2002-02-26
• Publisher: Elsevier Science

Summary

The Second Edition of Gene Therapy of Cancer provides crucial updates on the basic science and ongoing research in this field, examining the state of the art technology in gene therapy and its therapeutic applications to the treatment of cancer. The clinical chapters are improved to include new areas of research and more successful trials. Chapters emphasize the scientific basis of gene therapy using immune, oncogene, antisense, pro-drug activating, and drug resistance gene targets, while other chapters discuss therapeutic approaches and clinical applications. This book is a valuable reference for anyone needing to stay abreast of the latest advances in gene therapy treatment for cancer. Key Features * Provides in-depth description of targeted systems and treatment strategies * Explains the underlying cancer biology necessary for understanding a given therapeutic approach * Extensively covers immune therapeutics of vaccines, cytokines, and peptide-induced responses * Presents translational focus with emphasis on requirements for clinical implementation * Incorporates detailed illustrations of vectors and therapeutic approaches ideal for classroom presentations and general reference

Table of Contents

Contributors	xv
Preface	xix
PART I VECTORS FOR GENE THERAPY OF CANCER
Retroviral Vector Design for Cancer Gene Therapy
Christopher Baum
Wolfram Ostertag
Carol Stocking
Dorothee von Laer
Introduction	3	(1)
Applications for Retroviral Vectors in Oncology	4	(2)
Biology of Retroviruses	6	(3)
Principles of Retroviral Vector Systems	9	(2)
Advances in Retroviral Vector Tailoring	11	(11)
Outlook	22	(9)
References	23	(8)
Noninfectious Gene Transfer and Expression Systems for Cancer Gene Therapy
Mark J. Cooper
Introduction	31	(1)
Advantages and Disadvantages of Infectious, Viral-Based Vectors for Human Gene Therapy	31	(2)
Rationale for Considering Noninfectious, Plasmid-Based Expression Systems	33	(1)
Gene Transfer Technologies for Plasmid-Based Vectors: Preclinical Models and Clinical Cancer Gene Therapy Trials	33	(4)
Plasmid Expression Vectors	37	(6)
Future Directions	43	(10)
References	45	(8)
Parvovirus Vectors for the Gene Therapy of Cancer
K.K. Wong, Jr.
Saswati Chatterjee
Introduction	53	(1)
Biology of Parvoviridae and Vector Development	54	(7)
Applications of Recombinant Parvovirus Vectors to Cancer Gene Therapy	61	(10)
Perspectives, Problems, and Future Considerations	71	(10)
References	71	(10)
Antibody-Targeted Gene Therapy
C. Lampert
A. M. McCall
L.M. Weiner
Introduction	81	(1)
Background: Monoclonal Antibodies and Cancer Therapy	81	(3)
Recent Advances: Monoclonal-Antibody-Mediated Targeting and Cancer Gene Therapy	84	(7)
Future Directions	91	(4)
References	92	(3)
Ribozymes in Cancer Gene Therapy
Carmela Beger
Martin Kruger
Flossie Wong-Staal
Introduction	95	(1)
Ribozyme Structures and Functions	96	(2)
Cancer Disease Models for Ribozyme Application	98	(4)
Challenges and Future Directions	102	(7)
References	103	(6)
The Advent of Lentiviral Vectors: Prospects for Cancer Therapy
Michel Sadelain
Isabelle Riviere
Introduction	109	(1)
Structure and Function of Lentiviruses	110	(1)
Features that Distinguish Lentiviral from Oncoretroviral Vectors	111	(2)
Manufacture of Lentiviral Vectors	113	(4)
Possible Applications of Lentiviral Vectors in Cancer Therapy	117	(2)
Conclusions	119	(9)
References	120	(8)
PART II IMMUNE TARGETED GENE THERAPY
Immunologic Targets for the Gene Therapy of Cancer
Suzanne Ostrand-Rosenberg
Virginia K. Clements
Samudra Dissanayake
Mileka Gilbert
Beth A. Pulaski
Ling QI
Introduction	128	(1)
Cellular (T-Lymphocyte-Mediated) Versus Humoral (Antibody-Mediated) Immune Responses to Tumor Cells	128	(1)
Response of CD4+ and CD8+ T Lymphocytes to Tumor Antigens Presented in the Context of Molecules Encoded by the Major Histocompatibility Complex	129	(3)
Response of Tumor-Bearing Individuals to Tumor Antigens	132	(1)
Tumor-Associated Peptides as Candidate Targets for Tumor-Specific T Lymphocytes	133	(2)
Immunotherapeutic Strategies for the Treatment of Cancer	135	(3)
Conclusions	138	(7)
References	138	(7)
PART IIa VACCINE STRATEGIES
Development of Epitope-Specific Immunotherapies for Human Malignancies and Premalignant Lesions Expressing Mutated ras Genes
Scott I. Abrams
Introduction	145	(1)
Cellular Immune Response and Antigen Recognition	146	(1)
Pathways of Antigen Processing, Presentation, and Epitope Expression	146	(1)
T-Lymphocyte Subsets	147	(1)
ras Oncogenes in Neoplastic Development	147	(2)
Cellular Immune Responses Induced by ras Oncogene Peptides	149	(1)
Identification of Mutant ras CD4+ and CD8+ T-Cell Epitopes Reflecting Codon 12 Mutations	149	(7)
Anti-ras Immune System Interactions: Implications for Tumor Immunity and Tumor Escape	156	(2)
Paradigm for Anti-ras Immune System Interactions in Cancer Immunotherapy	158	(1)
Future Directions	159	(8)
References	160	(7)
PART IIb DENDRITIC CELL-BASED GENE THERAPY
Introduction to Dendritic Cells
Patrick Blanco
A. Karolina Palucka
Jacques Banchereau
Introduction	167	(1)
Features of Dendritic Cells	167	(2)
Dendritic Cell Subsets	169	(2)
Functional Heterogeneity of Dendritic Cell Subsets	171	(1)
Dendritic Cells in Tumor Immunology	172	(1)
Dendritic Cells and Gene Therapy	173	(1)
Conclusions	174	(5)
References	174	(5)
DNA and Dendritic Cell-Based Genetic Immunization Against Cancer
Lisa H. Butterfield
Antoni Ribas
James S. Economou
Introduction	179	(1)
Background	179	(4)
Recent Advances: Methods of Genetic Immunization	183	(7)
Preclinical Development and Translation to the Clinic	190	(1)
Proposed and Current Clinical Trials	190	(1)
Future Directions	191	(8)
References	191	(8)
RNA-Transfected Dendritic Cells as Immunogens
Michael A. Morse
Smita K. Nair
H. Kim Lyerly
Introduction	199	(1)
Advantages of Loading Dendritic Cells with Genetic Material	199	(1)
Viral Versus Nonviral Methods of Gene Transfer	200	(1)
RNA Versus DNA Loading of Dendritic Cells	200	(1)
RNA Loading of Dendritic Cells	201	(1)
Amplification of RNA Used to Load Dendritic Cells	201	(1)
Uses of RNA-Loaded Dendritic Cells	201	(1)
Future Directions	202	(5)
References	202	(5)
PART IIc CYTOKINES AND CO-FACTORS
In Situ Immune Modulation Using Recombinant Vaccinia Virus Vectors: Preclinical Studies to Clinical Implementation
Edmund C. Lattime
Laurence C. Eisenlohr
Leonard G. Gomella
Michael J. Mastrangelo
Introduction	207	(1)
Generation of Cell-Mediated Immune Responses	208	(2)
Cytokine Gene Transfer Studies in Antitumor Immunity	210	(1)
In Situ Cytokine Gene Transfer to Enhance Antitumor Immunity	210	(5)
Future Directions	215	(3)
Conclusions	218	(7)
References	219	(6)
The Use of Particle-Mediated Gene Transfer for Immunotherapy of Cancer
Mark R. Albertini
David M. King
Alexander L. Rakhmilevich
Introduction	225	(1)
Background	225	(3)
Recent Advances	228	(6)
Issues Regarding Evaluation in Clinical Trials	234	(1)
Recent Clinical Trials	234	(1)
Potential Novel Uses and Future Directions	235	(6)
References	235	(6)
PART IId GENETICALLY MODIFIED EFFECTOR CELLS FOR IMMUNE-BASED IMMUNOTHERAPY
Applications of Gene Transfer in the Adoptive Immunotherapy of Cancer
Kevin T. McDonagh
Alfred E. Chang
Introduction	241	(1)
Use of Gene-Modified Tumors to Generate Antitumor-Reactive T Cells	242	(4)
Genetic Manipulation of T Cells to Enhance Antitumor Reactivity	246	(4)
Genetic Modulation of Dendritic Cells	250	(1)
Summary	251	(6)
References	251	(6)
Update on the Use of Genetically Modified Hematopoietic Stem Cells for Cancer Therapy
Edsel U. Kim
Lee G. Wilke
James J. Mule
Introduction	257	(1)
Human Hematopoietic Stem Cells as Vehicles of Gene Transfer	258	(1)
Preclinical Studies of Gene Transfer into Hematopoietic Stem Cells	259	(3)
Applications of Genetically Manipulated Hematopoietic Stem Cells to the Therapy of Human Cancer	262	(6)
Conclusions	268	(5)
References	268	(5)
PART III ONCOGENE-TARGETED GENE THERAPY
Clinical Applications of Tumor-Suppressor Gene Therapy
Raymond D. Meng
Wafik S. El-Deiry
Introduction	273	(1)
p53	273	(2)
BRCAI	275	(1)
Onyx-015 Adenoviruses	275	(1)
Summary and Future Work	276	(3)
References	277	(2)
Cancer Gene Therapy with Tumor Suppressor Genes Involved in Cell-Cycle Control
Raymond D. Meng
Wafik S. El-Deiry
Introduction	279	(1)
p21WAFI/CIP1	280	(4)
p16INK4	284	(1)
Rb	285	(1)
p14ARF	286	(1)
p27Kip1	286	(1)
E2F-1	287	(1)
PTEN	288	(1)
BRCA1	288	(1)
VHL	289	(1)
FHIT	289	(1)
Apoptosis-Inducing Genes	289	(2)
Conclusions	291	(8)
References	291	(8)
Cancer Gene Therapy with the p53 Tumor Suppressor Gene
Raymond D. Meng
Wafik S. El-Deiry
Introduction	299	(1)
Vectors for Gene Therapy	300	(2)
p53	302	(6)
Conclusions	308	(7)
References	308	(7)
Antisense Downregulation of the Apoptosis-Related Bcl-2 and Bcl-xl Proteins: A New Approach to Cancer Therapy
Irina V. Lebedeva
C.A. Stein
The Bcl Family of Proteins and their Role in Apoptosis	315	(1)
Downregulation of Bcl-2 Expression: Antisense Strategies	316	(15)
References	324	(7)
Gene Therapy for Chronic Myelogenous Leukemia
Catherine M. Verfaillie
Robert Ch Zhao
Molecular Mechanisms Underlying Ph+ Leukemias	331	(1)
Therapy	331	(1)
Gene-Disruption Methods	332	(1)
Anti-bcr-abl Targeted Therapies	332	(1)
Anti-bcr-abl Drug-Resistance Gene Therapy for CML	332	(2)
Conclusion	334	(7)
References	334	(7)
PART IV MANIPULATION OF DRUG RESISTANCE MECHANISMS BY GENE THERAPY
Transfer of Drug-Resistance Genes into Hematopoietic Progenitors
Omer N. Koc
Steven P. Zielske
Justin C. Roth
Jane S. Reese
Stanton L. Gerson
Introduction	341	(1)
Rationale for Drug-Resistance Gene Therapy	342	(2)
Methyltransferase-Mediated Drug Resistance	344	(4)
Cytidine Deaminase	348	(1)
Glutathione-S-Transferase	348	(1)
Dual-Drug-Resistance Approach	349	(1)
Clinical Trials	350	(1)
Conclusion	351	(4)
References	351	(4)
Multidrug-Resistance Gene Therapy in Hematopoietic Cell Transplantation
Rafat Abonour
James M. Croop
Kenneth Cornetta
Introduction	355	(1)
P-Glycoprotein	356	(1)
Targeting Hematopoietic Progenitor Cells for Genetic Modification	356	(1)
Expression of P-Glycoprotein in Murine Hematopoietic Progenitors	357	(1)
Expression of P-Glycoprotein in Human Hematopoietic Progenitors	358	(1)
Results of Early Phase I Studies Using MDR1-Transduced Hematopoietic Cells	359	(1)
Overcoming Transduction Inefficiency	360	(1)
MDR1 Gene Transfer into Humans: Recent Progress	361	(1)
Implication and Future of MDR1 Gene Therapy in Humans	361	(4)
References	362	(3)
Development and Application of an Engineered Dihydrofolate Reductase and Cytidine-Deaminase-Based Fusion Genes in Myeloprotection-Based Gene Therapy Strategies
Owen A. O'Connor
Tulin Budak-Alpdogan
Joseph R. Bertino
Introduction	365	(3)
Fusion Genes	368	(2)
Development of Clinically Applicable Gene Transfer Approaches	370	(1)
Preclinical Evidence for Myeloprotection Strategies	371	(2)
Clinical Applications of Myeloprotection Strategies	373	(4)
Challenges	377	(6)
References	378	(5)
Protection from Antifolate Toxicity by Expression of Drug-Resistant Dihydrofolate Reductase
R. Scott McIvor
Introduction	383	(1)
Drug-Resistant Dihydrofolate Reductases	384	(1)
Protection from Antifolate Toxicity in Vitro	385	(1)
Protection from Antifolate Toxicity in Vivo: Retroviral Transduction Studies	386	(1)
Dihydrofolate Reductase Transgenic Mouse System for in Vivo Drug-Resistance Studies	386	(1)
Antitumor Studies in Animals Expressing Drug-Resistant Dihydrofolate Reductase	387	(1)
Antifolate-Mediated in Vivo Selection of Hematopoietic Cells Expressing Drug-Resistant Dihydrofolate Reductase	388	(1)
Summary and Future Considerations	388	(5)
References	389	(4)
A Genomic Approach to the Treatment of Breast Cancer
K.V. Chin
Deborah Toppmeyer
Thomas Kearney
Michael Reiss
Edmund C. Lattime
William N. Hait
Introduction	393	(1)
Toward a Genomic Approach to Therapy	393	(3)
The Use of DNA Microarrays to Understand Drug Resistance	396	(2)
Effects of Genomic-Based Approaches on the Management of Breast Cancer Patients	398	(7)
References	399	(6)
PART V ANTI-ANIOGENESIS AND PRO-APOPTOTIC GENE THERAPY
Antiangiogenic Gene Therapy
Steven K. Libutti
Andrew L. Feldman
Introduction	405	(1)
Angiogenesis and its Role in Tumor Biology	405	(1)
Antiangiogenic Therapy of Cancer and the Role of Gene Therapy	406	(1)
Preclinical Models of Antiangiogenic Gene Therapy	407	(5)
Inhibiting Proangiogenic Cytokines	412	(2)
Endothelial Cell-Specific Gene Delivery	414	(1)
Future Directions in Antiangiogenic Gene Therapy	415	(6)
References	415	(6)
VEGF-Targeted Antiangiogenic Gene Therapy
Calvin J. Kuo
Filip, A. Farnebo
Christian M. Becker
Judah Folkman
Introduction	421	(1)
Angiogenesis and Tumor Growth	422	(1)
Gene Therapy for Delivery of Antiangiogenic Factors	422	(1)
Antiangiogenic Gene Therapy in the Experimental and Clinical Settings	423	(1)
Vascular Endothelial Growth Factor and Receptors	423	(1)
Vascular Endothelial Growth Factor and Angiogenesis	424	(1)
Vascular Endothelial Growth Factor Inhibition by Gene Transfer	425	(3)
Issues Regarding Clinical Translation of Antiangiogenic Gene Therapy	428	(4)
Conclusion	432	(3)
References	432	(3)
Strategies for Combining Gene Therapy with Ionizing Radiation to Improve Antitumor Efficancy
David H. Gorski
Helena J. Mauceri
Ralph R. Weichselbaum
Introduction	435	(1)
Strategies Using Gene Therapy to Increase the Efficancy of Radiation Therapy	436	(4)
Enhancing the Replicative Potential of Antitumor Viruses with Ionizing Radiation	440	(1)
Transcriptional Targeting of Gene Therapy with Ionizing Radiation (Genetic Radiotherapy)	441	(2)
Summary and Future Directions	443	(6)
References	444	(5)
Virotherapy with Replication-Selective Oncolytic Adenoviruses: A Novel Therapeutic Platform for Cancer
David Kirn
Introduction	449	(2)
Attributes of Replication-Selective Adenoviruses for Cancer Treatment	451	(1)
Biology of Human Adenovirus	451	(1)
Mechanisms of Adenovirus-Mediated Cell Killing	451	(1)
Approaches to Optimizing Tumor-Selective Adenovirus Replication	452	(1)
Background: dl1520 (ONYX-015)	452	(1)
Clinical Trial Results with Wild-Type Adenovirus: Flawed Study Design	453	(1)
A Novel Staged Approach to Clinical Research with Replication-Selective Viruses: dl1520 (ONYX-015)	454	(1)
Results from Clinical Trials with dl1520 (ONYX-015)	455	(4)
Results from Clinical Trials with dl1520 (ONYX-015): Summary	459	(1)
Future Directions	460	(2)
Summary	462	(3)
References	462	(3)
E1A Cancer Gene Therapy
Duen-Hwa Yan
Ruping Shao
Mien-Chie Hung
Introduction	465	(1)
HER2 Overexpression and E1A-Mediated Anti-Tumor Activity	465	(2)
Mechanisms of E1A-Mediated Anti-Tumor Activity	467	(3)
E1A Gene Therapy: Preclinical Models	470	(2)
E1 A Gene Therapy: Clinical Trials	472	(1)
Conclusion	473	(8)
References	473	(8)
PART VI PRODRUG ACTIVATION STRATEGIES FOR GENE THERAPY OF CANCER
Preemptive and Therapeutic Uses of Suicide Genes for Cancer and Leukemia
Frederick L. Moolten
Paula J. Mroz
Introduction	481	(1)
Therapeutic Uses of Suicide Genes	482	(1)
Preemptive Uses of Suicide Genes in Cancer	483	(2)
Creation of Stable Suicide Functions by Combining Suicide Gene Transduction with Endogenous Gene Loss	485	(2)
Preemptive Uses of Suicide Genes to Control Graft-Versus-Host Disease in Leukemia	487	(1)
Future Prospects for Preemptive Use of Suicide Genes	488	(5)
References	489	(4)
Treatment of Mesothelioma Using Adenoviral-Mediated Delivery of Herpes Simplex Virus Thymidine Kinase Gene in Combination with Ganciclovir
Daniel H. Sterman
Steven M. Albelda
Introduction	493	(1)
Clinical Use of HSV-TK in the Treatment of Localized Malignancies	494	(5)
Challenges and Future Directions	499	(6)
References	501	(4)
The Use of Suicide Gene Therapy for the Treatment of Malignancies of the Brain
Kevin D. Judy
Stephen L. Eck
Introduction	505	(1)
Retrovirus Vector for HSV-TK	506	(3)
Adenovirus Vector for HSV-TK	509	(1)
Herpes Simplex Virus Vectors Expressing Endogenous HSV-TK	510	(1)
Promising Preclinical Studies	510	(3)
References	511	(2)
Case Study of Combined Gene and Radiation Therapy as an Approach in the Treatment of Cancer
Bin S. Teh
Maria T. Vlachaki
Laura K. Aguilar
Brian Miles
Gustavo Ayala
DOV Kadmon
Thomas Wheeler
Timothy C. Thompson
E. Brian Butler
Estuardo Aguilar-Cordova
Introduction	513	(1)
Background of the Field	514	(1)
Recent Advances in Herpes Simplex Virus-Thymidine Kinase Suicide Gene Therapy	515	(1)
Combined Herpes Simplex Virus-Thymidine Kinase Suicide Gene Therapy and Radiotherapy	516	(5)
Issues Regarding Clinical Trials, Translation into Clinical Use, Preclinical Development, Efficacy, Endpoints, and Gene Expression	521	(1)
Potential Novel Uses and Future Directions	522	(3)
References	523	(2)
Index	525