Development of immunotherapeutic strategies for the treatment of malignant neoplasms.

Focused preclinical studies have been used to gain insight into the mechanism of therapeutic activity of cytokines, growth factors and biological response modifiers (BRMs). These data can then be used to develop a clinical hypothesis to facilitate the development of these new biological drugs. In this manuscript, we discuss a number of preclinical and clinical studies using interferon-gamma, IL-2, and the colony stimulating factors. The importance of the systematic profiling of the biological activity of such biological drugs is emphasized and we discuss the utility of the mechanistic data in their clinical development. The overall preclinical approach identifies the cellular, biochemical or gene regulatory event that is associated with the therapeutic activity of a biologic and this surrogate (be it biological, chemical, or quality of life) is then used to optimize the clinical protocol in a phase 1b trial. This, in theory, results in the rapid identification of the optimal dose, schedule and route of administration for subsequent testing in a phase II/III clinical trial.