Since the discovery of the molecular structure of genes and the unveiling of the molecular basis of numerous human diseases, scientists have been fas- nated with the possibility of treating certain diseases by transducing foreign DNA into the affected cells. Initially, it was proposed that the foreign DNA could either replace defective nonfunctional genes, or code for therapeutic proteins. This concept has evolved into the rapidly growing field of gene therapy. Even though surgery, radiotherapy, and chemotherapy are widely ava- able and routinely used for cancer treatment, these therapies fail to cure approximately 50 percent of cancer patients. Therefore, since it is a disease characterized by aberrant gene expression, cancer has been a target of gene therapy research since the inception of this treatment modality. Numerous cancer gene therapy strategies are currently being investigated, including gene replacement therapy, the regulation of gene expression to modulate immu- logical responses to tumors, the direct killing of tumor cells, and direct int- ference with tumor growth. In this context, gene transfer systems, tumor-specific expression vectors, and novel therapeutic genes have been extensively st- ied. All these strategies aim for the selective destruction of human malignant disease while circumventing the destruction of nonmalignant cells and tissues thereby minimizing toxicity to the patient.

Part I. Experimental Approaches to Cancer Gene Therapy. Immunotherapy/ Tumor vaccination. Immunizing Potential of Cytokine-Transduced Tumor Cells. Particle-Mediated Gene Transfer into Dendritic Cells: A Novel Strategy for the Induction of Immune Responses against Tumor Antigens. Cancer Gene Therapy with Heat Shock Protein-65 Gene. Recombinant Vaccinia Virus MVA for Generation and Analysis of T Cell Responses Against Tumor Associated Antigens. Suicide Gene Therapy. Selection of Cytochrome P450 Genes for Use in Prodrug Activation-Based Cancer Gene Therapy. Construction of P450-Expressing Tumor Cell Lines Using Retroviruses. In Vitro Methods for Evaluation of P450-Based Anticancer Gene Therapy. Tumor Models for Evaluation of P450 Gene Therapy In Vivo. Anti-Oncogene and Suppressor Gene Therapy. Intracellular Single-Chain Antibodies for Gene Therapy. Combined Adenoviral Transfer of Tumor Suppressor and Cell-Cycle Genes for Tumor-Cell Apoptosis. Antisense Gene Therapy. Inhibition of Cell Growth by Antisense Oligonucleotides Targeting the Growth-Related Protein Kinase c-raf. IGF-1 Antisense Strategies for Cancer Treatment. Ribozyme Gene Therapy. Anti-MDR1 Ribozyme Gene Therapy. Anti-c-erbB2 Ribozyme for Gene Therapy of Breast Cancer. Anti-K-ras Ribozyme Adenoviral Vector for Gene Therapy of Non-Small Cell Lung Cancer. Delivery Systems and Tumor Targeting. Green Fluorescent Protein Retroviral Vector: Generation of High-Titer Producer Cells and Virus Supernatant. HSV-1 Vectors for Gene Therapy of Experimental CNS Tumors. Intratumoral Injection of Naked DNA. Cationic Liposome Gene Transfer. In Vivo Particle-Mediated Gene Transfer for Cancer Therapy. Gene Targeting to Hepatomas (AFP). Adenovirus-Mediated Targeted Gene Therapy for Breast Cancer and for Purging Hematopoietic Stem-Cell Sources. Chemotherapy-Inducible Vector for Gene Therapy of Cancer. Alternative Approaches in Cancer Gene Therapy. Oncolytic Adenoviral Vectors. Genetically Modified Clostridium for Gene Therapy of Tumors. Tumor-Targeted Salmonella: Strain Development and Expression of the HSV-tK Effector Gene. Part II. Clinical Protocols for Cancer Gene Therapy. Immunotherapy/Tumor Vaccination. Ex Vivo Cytokine Gene Transfer in Melanomas by Using Particle Bombardment. Intratumoral Gene Transfer of the HLA-B7 Gene Into Colon Carcinoma Metastases. Hybrid Cell Vaccination in Patients with Metastatic Melanoma. Suicide Gene Therapy. Retroviral Transfer of the Herpes Simplex Virus-Thymidine Kinase (HSV-tK) Gene for the Treatment of Cancer. Gene Therapy for Treatment of Brain Tumors (HSV-tK In Vivo Gene Transfer): A Case Study. Gene Therapy of Glioblastoma Multiforme with a Bicistronic Retroviral Vector Expressing Human IL-2 and HSV-tk. Intratumoral Gene Transfer of the Cytosine Deaminase Gene for the Treatment of Breast Cancer. Anti-Oncogene and Suppressor Gene Therapy. Adenovirus-Mediated Wild-Type p53 Gene Transfer into Head and Neck Cancers. Direct DNA Injection (p53) into HCC Tumors. A Phase II Trial of Intratumoral Injection with Selectively Replicating Adenovirus (ONYX-015) in Patients with Recurrent, Refractory Squamous Cell Carcinoma of the Head and Neck. Antisense Gene Therapy. c-myb Antisense Oligonucleotide Therapeutics for Hematologic Malignancies. Ovarian Cancer Gene Therapy with BRCA1- An Overview. Methods for Chemoprotection and Chemosensitization: MDR-1 For Chemoprotection Using Retroviruses to Modify Hematopoietic Cells and Cytosine Deaminase for Chemosensitization Using Adenoviral Vectors to Modify Epithelian Neoplastic Cells. Index

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