Experimental design for the evaluation of the antitumor action of cytokines.

Cytokines are cellular proteins capable of exerting a variety of different biological effects both in vitro and in vivo. The availability of large amounts of recombinant highly purified cytokines now allows clinicians to explore the possible therapeutic use of these molecules. Some of these cytokines (such as interferons, "tumor necrosis factor" and interleukin-2) have been widely shown to exert antitumor effects in animal model systems and are now used in clinical trials to treat cancer patients. However, the mechanisms of these antitumor effects are poorly understood. In view of their multiple biological properties it appears very important to define suitable experimental systems for studying the antitumor effects of cytokines. In fact, one of the major problems facing researchers involved in the cytokine field is to evaluate the relevance of the different biological effects observed in in vitro cell systems with respect to the antitumor effects observed in vivo. Tumor bearing-mice injected with transplantable tumor cells can represent unique, preclinical, experimental systems to study the mechanisms of antitumor action of cytokines. In fact, only by combining the information derived from in vitro cell systems with data obtained from suitable animal models it is possible to achieve relevant insights on the mechanisms of antitumor action of cytokines. Such in vitro and in vivo studies should represent a basic support for a better use of cytokines in clinical trials with cancer patients. In this article we review the major mouse models for studying the mechanisms of antitumor action of cytokines. Furthermore, we briefly summarize our data on the antitumor effects of cytokines in mice injected with transplantable Friend leukemia cells and we discuss the advantages and the disadvantages in choosing specific animal models for studying the antitumor effects of cytokines.