Gene Therapy of Cancer

Gene Therapy of Cancer : Translational Approaches from Preclinical Studies to Clinical Implementation

List price: US$275.01

Currently unavailable

Add to wishlist

AbeBooks may have this title (opens in new window).

Try AbeBooks


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.
show more

Product details

  • Hardback | 534 pages
  • 220 x 282 x 26mm | 1,519.53g
  • Academic Press Inc
  • San Diego, United States
  • English
  • 2nd edition
  • colour and b&w illustrations
  • 0124375510
  • 9780124375512

About Edmund C. Lattime

Edmund C. Lattime is currently with Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, The Cancer Institute of New Jersey. He received his Ph.D. at Rutgers University and has a Postdoctoral Fellow (Cellular Immunology) from Sloan-Kettering Institute for Cancer. Dr. Lattime has been given a Young Investigator Award from the National Cancer Institute and a Scholar Award from the Leukemia Society of America. He is a member of several editorial boards and review committees, and is currently an academic advisor to the University of Michigan's "Genetic Approaches for Cancer Immunotherapy" Committee. He has been a corporate advisor to Schering-Plough's Bladder Cancer Advisory Board, and has written or contributed to many papers, articles and book chapters. Lattime is also a sought-after lecturer, having been invited to speak at many universities and conferences. 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.
show more

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


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


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


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


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


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


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



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


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


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


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



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


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



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


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


Part III Oncogene-Targeted Gene Therapy

16. Clinical Applications of Tumor-Suppressor Gene Therapy

I. Introduction

II. p53


IV. Onyx-015 Adenoviruses

V. Summary and Future Work


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





XII. Apoptosis-Inducing Genes

XIII. Conclusions


18. Cancer Gene Therapy with the p53 Tumor Suppressor Gene

I. Introduction

II. Vectors for Gene Therapy

III. p53

IV. Conclusions


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


show more

Review quote

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
show more

Review Text

" ...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)
show more