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.