Overview

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.

Full Product Details

Author:   Edmund C. Lattime ,  Stanton L. Gerson
Publisher:   Elsevier Science Publishing Co Inc
Imprint:   Academic Press Inc
Edition:   2nd edition
Dimensions:   Width: 21.60cm , Height: 2.70cm , Length: 27.90cm
Weight:   1.520kg
ISBN:  

9780124375512

ISBN 10:   0124375510
Pages:   534
Publication Date:   04 April 2002
Audience:   Professional and scholarly ,  Professional & Vocational
Replaced By:   9780123942951
Format:   Hardback
Publisher's Status:   Active
Availability:   Temporarily unavailable  
The supplier advises that this item is temporarily unavailable. It will be ordered for you and placed on backorder. Once it does come back in stock, we will ship it out to you.

Table of Contents

Part I Vectors for Gene Therapy of Cancer 1. Retroviral Vector Design for Cancer Gene Therapy I. Introduction II. Applications for Retroviral Vectors in Oncology III. Biology of Retroviruses IV. Principles of Retroviral Vector Systems V. Advances in Retroviral Vector Tailoring VI. Outlook References 2. Noninfectious Gene Transfer and Expression Systems for Cancer Gene Therapy I. Introduction II. Advantages and Disadvantages of Infectious, Viral-Based Vectors for Human Gene Therapy III. Rationale for Considering Noninfectious, Plasmid-Based Expression Systems IV. Gene Transfer Technologies for Plasmid-Based Vectors: Preclinical Models and Clinical Cancer Gene Therapy Trials V. Plasmid Expression Vectors VI. Future Directions References 3. Parvovirus Vectors for the Gene Therapy of Cancer I. Introduction II. Biology of Parvoviridae and Vector Development III. Applications of Recombinant Parvovirus Vectors to Cancer Gene Therapy IV. Perspectives, Problems, and Future Considerations References 4. Antibody-Targeted Gene Therapy I. Introduction II. Background: Monoclonal Antibodies and Cancer Therapy III. Recent Advances: Monoclonal-Antibody-Mediated Targeting and Cancer Gene Therapy IV. Future Directions References 5. Ribozymes in Cancer Gene Therapy I. Introduction II. Ribozyme Structures and Functions III. Cancer Disease Models for Ribozyme Application IV. Challenges and Future Directions References 6. The Advent of Lentiviral Vectors: Prospects for Cancer Therapy I. Introduction II. Structure and Function of Lentiviruses III. Features that Distinguish Lentiviral from Oncoretroviral Vectors IV. Manufacture of Lentiviral Vectors V. Possible Applications of Lentiviral Vectors in Cancer Therapy VI. Conclusions References Part II Immune Targeted Gene Therapy 7. Immunologic Targets for the Gene Therapy of Cancer I. Introduction II. Cellular (T-Lymphocyte-Mediated) Versus Humoral (Antibody-Mediated) Immune Responses to Tumor Cells III. Response of CD4+ and CD8+ T Lymphocytes to Tumor Antigens Presented in the Context of Molecules Encoded by the Major Histocompatibility Complex IV. Response of Tumor-Bearing Individuals to Tumor Antigens V. Tumor-Associated Peptides as Candidate Targets for Tumor-Specific Lymphocytes VI. Immunotherapeutic Strategies for the Treatment of Cancer VII.Conclusions References Part IIa Vaccine Strategies 8. Development of Epitope-Specific Immunotherapies for Human Malignancies and Premalignant Lesions Expressing Mutated ras Genes I. Introduction II. Cellular Immune Response and Antigen Recognition III. Pathways of Antigen Processing, Presentation, and Epitope Expression IV. T-Lymphocyte Subsets V. ras Oncogenes in Neoplastic Development VI. Cellular Immune Responses Induced by ras Oncogene Peptides VII. Identification of Mutant ras CD4+ and CD8+ T-Cell Epitopes Reflecting Codon 12 Mutations VIII. Anti-ras Immune System Interactions: Implications for Tumor Immunity and Tumor Escape IX. Paradigm for Anti-ras Immune System Interactions in Cancer Immunotherapy X. Future Directions References Part IIb Dendritic Cell-Based Gene Therapy 9. Introduction to Dendritic Cells I. Introduction II. Features of Dendritic Cells III. Dendritic Cell Subsets IV. Functional Heterogeneity of Dendritic Cell Subsets V. Dendritic Cells in Tumor Immunology VI. Dendritic Cells and Gene Therapy VII. Conclusions References 10. DNA and Dendritic Cell-Based Genetic Immunization Against Cancer I. Introduction II. Background III. Recent Advances: Methods of Genetic Immunization IV. Preclinical Development and Translation to the Clinic V. Proposed and Current Clinical Trials VI. Future Directions References 11. RNA-Transfected Dendritic Cells as Immunogens I. Introduction II. Advantages of Loading Dendritic Cells with Genetic Material III. Viral Versus Nonviral Methods of Gene Transfer 200 IV. RNA Versus DNA Loading of Dendritic Cells V. RNA Loading of Dendritic Cells VI. Amplification of RNA Used to Load Dendritic Cells VII. Uses of RNA-Loaded Dendritic Cells VIII. Future Directions References PART IIc CYTOKINES AND CO-FACTORS 12. In Situ Immune Modulation Using Recombinant Vaccinia Virus Vectors: Preclinical Studies to Clinical Implementation I. Introduction II. Generation of Cell-Mediated Immune Responses III. Cytokine Gene Transfer Studies in Antitumor Immunity IV. In Situ Cytokine Gene Transfer to Enhance Antitumor Immunity V. Future Directions VI. Conclusions References 13. The Use of Particle-Mediated Gene Transfer for Immunotherapy of Cancer I. Introduction II. Background III. Recent Advances IV. Issues Regarding Evaluation in Clinical Trials V. Recent Clinical Trials VI. Potential Novel Uses and Future Directions References PART IId GENETICALLY MODIFIED EFFECTOR CELLS FOR IMMUNE-BASED IMMUNOTHERAPY 14. Applications of Gene Transfer in the Adoptive Immunotherapy of Cancer I. Introduction II. Use of Gene-Modified Tumors to Generate Antitumor-Reactive T Cells III. Genetic Manipulation of T Cells to Enhance Antitumor Reactivity IV. Genetic Modulation of Dendritic Cells V. Summary References 15. Update on the Use of Genetically Modified Hematopoietic Stem Cells for Cancer Therapy I. Introduction II. Human Hematopoietic Stem Cells as Vehicles of Gene Transfer III. Preclinical Studies of Gene Transfer into Hematopoietic Stem Cells IV. Applications of Genetically Manipulated Hematopoietic Stem Cells to the Therapy of Human Cancer V. Conclusions References Part III Oncogene-Targeted Gene Therapy 16. Clinical Applications of Tumor-Suppressor Gene Therapy I. Introduction II. p53 III. BRCA1 IV. Onyx-015 Adenoviruses V. Summary and Future Work References 17. Cancer Gene Therapy with Tumor Suppressor Genes Involved in Cell-Cycle Control I. Introduction II. p21WAF1/CIP1 III. p16INK4 IV. Rb V. p14ARF VI. p27Kip1 VII. E2F-1 VIII. PTEN IX. BRCA1 X. VHL XI. FHIT XII. Apoptosis-Inducing Genes XIII. Conclusions References 18. Cancer Gene Therapy with the p53 Tumor Suppressor Gene I. Introduction II. Vectors for Gene Therapy III. p53 IV. Conclusions References 19. Antisense Downregulation of the Apoptosis-Related Bcl-2 and Bcl-xl Proteins: A New Approach to Cancer Therapy I. The Bcl Family of Proteins and their Role in Apoptosis II. Downregulation of Bcl-2 Expression: Antisense Strategies References 20. Gene Therapy for Chronic Myelogenous Leukemia I. Molecular Mechanisms Underlying Ph+ Leukemias II. Therapy III. Gene-Disruption Methods IV. Anti-bcr-abl Targeted Therapies V. Anti-bcr-abl Drug-Resistance Gene Therapy for CML VI. Conclusion References Part IV Manipulation of Drug Resistance Mechanisms by Gene Therapy 21. Transfer of Drug-Resistance Genes into Hematopoietic Progenitors I. Introduction II. Rationale for Drug-Resistance Gene Therapy III. Methyltransferase-Mediated Drug Resistance IV. Cytidine Deaminase V. Glutathione-S-Transferase VI. Dual-Drug-Resistance Approach VII. Clinical Trials VIII. Conclusion References 22. Multidrug-Resistance Gene Therapy in Hematopoietic Cell Transplantation I. Introduction II. P-Glycoprotein III. Targeting Hematopoietic Progenitor Cells for Genetic Modification IV. Expression of P-Glycoprotein in Murine Hematopoietic Progenitors V. Expression of P-Glycoprotein in Human Hematopoietic Progenitors VI. Results of Early Phase I Studies Using MDR1-Transduced Hematopoietic Cells VII. Overcoming Transduction Inefficiency VIII. MDR1 Gene Transfer into Humans: Recent Progress IX. Implication and Future of MDR1 Gene Therapy in Humans References 23. Development and Application of an Engineered Dihydrofolate Reductase and Cytidine-Deaminase-Based Fusion Genes in Myeloprotection-Based Gene Therapy Strategies I. Introduction II. Fusion Genes III. Development of Clinically Applicable Gene Transfer Approaches IV. Preclinical Evidence for Myeloprotection Strategies V. Clinical Applications of Myeloprotection Strategies VI. Challenges References 24. Protection from Antifolate Toxicity by Expression of Drug-Resistant Dihydrofolate Reductase I. Introduction II. Drug-Resistant Dihydrofolate Reductases III. Protection from Antifolate Toxicity In Vitro IV. Protection from Antifolate Toxicity In Vivo: Retroviral Transduction Studies V. Dihydrofolate Reductase Transgenic Mouse System for In Vivo Drug-Resistance Studies VI. Antitumor Studies in Animals Expressing Drug-Resistant Dihydrofolate Reductase VII. Antifolate-Mediated In Vivo Selection of Hematopoietic Cells Expressing Drug-Resistant Dihydrofolate Reductase VIII. Summary and Future Considerations References 25. A Genomic Approach to the Treatment of Breast Cancer I. Introduction II. Toward a Genomic Approach to Therapy III. The Use of DNA Microarrays to Understand Drug Resistance IV. Effects of Genomic-Based Approaches on the Management of Breast Cancer Patients References Part V Anti-Aniogenesis and Pro-Apoptotic Gene Therapy 26. Antiangiogenic Gene Therapy I. Introduction II. Angiogenesis and its Role in Tumor Biology III. Antiangiogenic Therapy of Cancer and the Role of Gene Therapy IV. Preclinical Models of Antiangiogenic Gene Therapy V. Inhibiting Proangiogenic Cytokines VI. Endothelial Cell-Specific Gene Delivery VII. Future Directions in Antiangiogenic Gene Therapy References 27. VEGF-Targeted Antiangiogenic Gene Therapy I. Introduction II. Angiogenesis and Tumor Growth III. Gene Therapy for Delivery of Antiangiogenic Factors IV. Antiangiogenic Gene Therapy in the Experimental and Clinical Settings V. Vascular Endothelial Growth Factor and Receptors VI. Vascular Endothelial Growth Factor and Angiogenesis VII. Vascular Endothelial Growth Factor Inhibition by Gene Transfer VIII. Issues Regarding Clinical Translation of Antiangiogenic Gene Therapy IX. Conclusion References 28. Strategies for Combining Gene Therapy with Ionizing Radiation to Improve Antitumor Efficacy I. Introduction II. Strategies Using Gene Therapy to Increase the Efficacy of Radiation Therapy III. Enhancing the Replicative Potential of Antitumor Viruses with Ionizing Radiation IV. Transcriptional Targeting of Gene Therapy with Ionizing Radiation (Genetic Radiotherapy) V. Summary and Future Directions References 29. Virotherapy with Replication-Selective Oncolytic Adenoviruses: A Novel Therapeutic Platform for Cancer I. Introduction II. Attributes of Replication-Selective Adenoviruses for Cancer Treatment III. Biology of Human Adenovirus IV. Mechanisms of Adenovirus-Mediated Cell Killing V. Approaches to Optimizing Tumor-Selective Adenovirus Replication VI. Background: dl1520 (ONYX-015) VII. Clinical Trial Results with Wild-Type Adenovirus: Flawed Study Design VIII. A Novel Staged Approach to Clinical Research with Replication-Selective Viruses: dl1520 (ONYX-015) IX. Results from Clinical Trials with dl1520 (ONYX-015) X. Results from Clinical Trials with dl1520 (ONYX-015): Summary XI. Future Directions XII. Summary References 30. E1A Cancer Gene Therapy I. Introduction II. HER2 Overexpression and E1A-Mediated Antitumor Activity III. Mechanisms of E1A-Mediated Anti-Tumor Activity IV. E1A Gene Therapy: Preclinical Models V. E1A Gene Therapy: Clinical Trials VI. Conclusion References Part VI Prodrug Activation Strategies for Gene Therapy of Cancer 31. Preemptive and Therapeutic Uses of Suicide Genes for Cancer and Leukemia I. Introduction II. Therapeutic Uses of Suicide Genes III. Preemptive Uses of Suicide Genes in Cancer IV. Creation of Stable Suicide Functions by Combining Suicide Gene Transduction with Endogenous Gene Loss V. Preemptive Uses of Suicide Genes to Control Graft-Versus-Host Disease in Leukemia VI. Future Prospects for Preemptive Use of Suicide Genes References 32. Treatment of Mesothelioma Using Adenoviral-Mediated Delivery of Herpes Simplex Virus Thymidine Kinase Gene in Combination with Ganciclovir I. Introduction II. Clinical Use of HSV-TK in the Treatment of Localized Malignancies III. Challenges and Future Directions References 33. The Use of Suicide Gene Therapy for the Treatment of Malignancies of the Brain I. Introduction II. Retrovirus Vector for HSV-TK III. Adenovirus Vector for HSV-TK IV. Herpes Simplex Virus Vectors Expressing Endogenous HSV-TK V. Promising Preclinical Studies References 34. Case Study of Combined Gene and Radiation Therapy as an Approach in the Treatment of Cancer I. Introduction II. Background of the Field III. Recent Advances in Herpes Simplex Virus-Thymidine Kinase Suicide Gene Therapy IV. Combined Herpes Simplex Virus-Thymidine Kinase Suicide Gene Therapy and Radiotherapy V. Issues Regarding Clinical Trials, Translation into Clinical Use, Preclinical Development, Efficacy, Endpoints, and Gene Expression VI. Potential Novel Uses and Future Directions

Reviews

Review of First Edition: ...offers a comprehensive review of the rapidly evolving field of cancer gene therapy for basic, translational, and clinical scientists. The editors have assembled a distinguished group of academic contributors... Their insights into the progress of cancer gene therapy and the challenges ahead are thoughtful and provocative. - GYNECOLOGIC ONCOLOGY

Review of First Edition: ...offers a comprehensive review of the rapidly evolving field of cancer gene therapy for basic, translational, and clinical scientists. The editors have assembled a distinguished group of academic contributors... Their insights into the progress of cancer gene therapy and the challenges ahead are thoughtful and provocative. - GYNECOLOGIC ONCOLOGY

...represents the 'state-of-the-art', describing the progress made to date in its written chapters. ...this book is a worthy addition to the laboratories and libraries serving the students, fellows and experienced researchers devoted to translating cancer gene therapy applications from laboratory to the bedside. @source-Robert E. Sobol, GenStar Therapeutics, Sidney Kimmel Cancer Center (2002)

Author Information

Edmund C. Lattime is Professor of Surgery at the Robert Wood Johnson Medical School and Deputy Director, The Cancer Institute of New Jersey. Dr. Lattime studies tumor immunology and immunotherapy focusing on the tumor-host interaction and the tumor microenvironment. While faculty at Sloan Kettering and then Thomas Jefferson University, his translational studies led to the development and Phase I testing of a novel Vaccinia-GMCSF construct designed to enhance the development of antitumor immunity via infection/transfection of the tumor microenvironment. Based on his mechanistic studies of immune escape mechanisms, his group recently developed and is testing a poxvirus-based immunization strategy, which uses antigen encoding poxvirus delivered to the tumor microenvironment, in patients with locally-advanced pancreatic cancer. Stanton L Gerson is Director of the Case Comprehensive Cancer Center & the National Center for Regenerative Medicine at Case Western Reserve University and Director of University Hospitals Seidman Cancer Center in Cleveland. Dr. Gerson studies DNA repair, stem cells and cancer therapy. He showed that over-expression of the MGMT DNA repair gene could prevent cancer and that a mutant form of MGMT protects hematopoietic stem cells from chemotherapy using lentiviral gene therapy. He has interrogated MGMT, MMR and BER DNA repair pathways as targets for cancer therapy, and proposed that methoxyamine would block base excision repair used in combination with chemotherapy. Dr. Gerson also directed the initial use of mesenchymal stem cells (MSCs) in bone marrow transplantation & in gene therapy. Stanton L. Gerson received his M.D. at Harvard Medical School. He was a Resident in Medicine at the Hospital of the University of Pennsylvania, where he became a Fellow in Hematology-Oncology in 1980. He is an Edward Mallinckrodt Jr. Foundation Scholar, and is currently Chief, Division of Hematology/Oncology at Case Western Reserve Univeristy, where he has served since 1983. Dr. Gerson is a member of several major professional and scientific societies and is a principal investigator of funded grants for several philanthropic organizations. He is author or a contributor to over 200 research papers, abstracts, theses and book chapters. Since 1987, Dr. Gerson has been invited to be a guest lecturer at over 40 national and international conferences.

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