Combination Therapies : Biological Response Modifiers in the Treatment of Cancer and Infectious Diseases

Over the past decade many of the key lymphokines, hormones and growth factors that help regulate the immune system have been defined. These molecules, termed biological response modifiers (BRMs) , have been sequenced, synthesized and produced in large enough quantities to test in animals and humans resulting in the development of new approaches to the treatment of human disease, in particular, cancers and infectious diseases. Advances in this area have also led to rethinking therapies against a range of autoimmune disorders and other diseases associated with immune and endocrine imbalances. BRMs currently are being applied clinically as both primary and adjunctive therapy to enhance the effectiveness of traditional treatments by maximizing their activities and to protect critical tissues against intolerable chemotherapeutic and radiation damage. Present constraints against the use of BRMs revolve around the nature of these substances in vivo, where many of their actions and the majority of their interactions and synergies remain to be elucidated. For example, as these molecules are thought to exert their effects locally, the systemic administration of lymphokines, cytokines and growth factors at doses adequate to produce a wanted anti-tumor effect in many instances is intolerably toxic. Efforts to overcome this formidable problem have led scientists to begin to explore the transfer of genes known to encode for these molecules into cells which otherwise inadequately elicit or produce anti-tumor or anti-infective responses. Front Matter....Pages i-xv Front Matter....Pages 1-1 Combination Therapy with Thymic Hormones and Cytokines after Chemotherapy in Cancer Treatment....Pages 1-12 Immune Therapy of Human Cancers....Pages 13-17 Use of IL-2 and Lymphocytes Following Bone Marrow Transplantation....Pages 19-28 COMBO: New Concepts and Methods for Designing and Analyzing Experiments on Combination Therapy....Pages 29-38 Combinations of Lymphocyte Activating Agents for Expansion of Tumor Infiltrating Lymphocytes from Renal Cell Carcinoma....Pages 39-48 Front Matter....Pages 49-49 IL-2 Based Combination Therapy of Malignant Disease: Summary of the Phase I Experience at the Cleveland Clinic....Pages 49-55 The Role of Combination Biologic Therapy in the Immunotherapeutic Approach to the Treatment of Renal Cell Carcinoma....Pages 57-65 Maintenance Treatment with Recombinant Interferon Alfa-2b Prolongs Remission and Survival in Patients with Multiple Myeloma Responding to Induction Chemotherapy....Pages 67-72 Combination of Fluorouracil and Interferon: Mechanisms of Interaction and Clinical Studies....Pages 73-78 Combination Chemotherapy and Cytokines in the Treatment of Advanced Primary Lung Cancer: Controlled Clinical Trial Three Year Results....Pages 79-85 Tumor Immunotherapy with Combined Interleukins Injected Perilymphatically: Experimental and Clinical Findings....Pages 87-96 Front Matter....Pages 97-97 Combination Therapies with Cytokines and Anti-Cytokines in Murine Opportunistic Infections....Pages 97-104 Treatment and Pharmacokinetics of Liposomal-Amphotericin B Patients with Systemic Fungal Infections....Pages 105-112 The Potential Role of Immunomodulation in the Treatment of HIV-Infection and Malignant Diseases....Pages 113-122 Use of Drugs Targeted to Inhibit Different Stages of the HIV Life Cycle in the Treatment of AIDS....Pages 123-129 Aspirin as a Biological Response Modifier....Pages 131-137 Biological Therapies in Geriatric Populations....Pages 139-147 Thymosin: An Innovative Approach to the Treatment of Chronic Hepatitis B....Pages 149-157 Cell Wall Constituents of Candida Albicans as Biological Response Modifiers....Pages 159-166 Cytokines Modulate HIV Replication and the Activity of Antiviral Drugs in Cells of Monocyte/Macrophage Lineage....Pages 167-176 Front Matter....Pages 177-177 The Case for Synergy of Thymic Hormones and Interleukins in Immune Reconstitution....Pages 177-184 Inducing Immunity to Human Melanoma Cells: Opening the Bag of Immunological Tricks....Pages 185-188 Immune Mediated Tumor Destruction: Challenges for the 1990’s....Pages 189-195 Abnormal Immunoregulation in Human Cancer at the Actual Tumor Site....Pages 197-206 The Immunobiology of Human Macrophage Fc γ Receptors....Pages 207-214 Synergy between G-CSF and WR-2721: Effects on Enhancing Hemopoietic Reconstitution and Increasing Survival Following Exposure to Ionizing Radiation....Pages 215-222 ST 789, A Candidate for Combination Therapies of Infections and Cancer....Pages 223-229 QS-21 Augments the Antibody Response to a Synthetic Peptide Vaccine Compared to Alum....Pages 231-236 Synergistic Regulation of Lak Lymphocyte Cytotoxicity by Combination Cytokine and Cisplatin Treatment....Pages 237-244 The Biological Response Modifiers Interleukin-2 and Tumor Necrosis Factor-α Modulate the Cytotoxic Activity of Tumor Infiltrating Lymphocytes Against Human Colon Cancer Cells....Pages 245-251 Isolation and Chemical Characterization of a Novel Thymic Hormone that Synergizes with GRF and TRH in Enhancing Release of Growth Hormone and Prolactin....Pages 253-267 Front Matter....Pages 269-269 Cytokine-Based Combined Modality Approaches to the Treatment of Murine Renal Cancer....Pages 269-274 Rationale for Therapeutic Approaches with Thymosin α 1, Interleukin 2 and Interferon in Combination with Chemotherapy....Pages 275-281 Mechanisms of Combined IL-1/IL-2 and IL-1/IFN Therapy in Mice Injected with Metastatic Tumor Cells....Pages 283-291 Cancer Immunotherapy: Preclinical Studies with Triazene Compounds....Pages 293-301 Back Matter....Pages 303-313 Combination Immunotherapy: Immune Therapy of Human Cancers (R.P. Gale, A. Butturini). Clinical Applications of Combination Chemoimmunotherapy in Cancer: Combination of Fluorouracil and Interfon (R. Pazdur). Combination Approaches and Gene Therapy in the Treatment of AIDS and Other Infectious Diseases: Combination Therapies with Cytokines and AntiCytokines in Murine Opportunistic Infections (L. Romani et al.). Mechanism of Action and Synergy Between Drugs, Biological Response Modifiers and/or Vaccines in Combination Therapies: The Case for Synergy of Thymic Hormones and Interle