Workshop Summary: Animal Tumor Models for Evaluating Chemically Defined Immunomodulators

Abstract

Efforts to establish an immunopharmacology for cancer immunotherapy have been frustrated by the lack of animal tumor models which directly relate to human cancer. Initially, emphasis was placed on transplantable tumors which were often inadvertently immunogenic by nature of infection with murine viruses or were of nonsyngeneic origins. The easily demonstrated effectiveness of BCG, C. parvum and high molecular weight polysaccharide preparations led to the erroneous conclusion that such therapy in man would be equally effective. Considerable clinical trials since have not generally supported this conclusion. The relative failure of these agents in the human can be attributed to a number of factors including the inadequacy of the models. Complexity and ambivalence of their actions in humans have played a major role. The evolution of immunotherapy in human cancer has increasingly moved away from the complex agents towards the use of biologicals and chemically defined agents. It is clear that seldom are the agents effective in cancer therapy when used as a monotherapy. The apparent rule, both in murine tumor systems and in human cancer trials, has emerged that these agents act to increase the number of individuals remaining in remission following effective cytoreductive therapy with chemotherapy, surgery or irradiation. They have not been particularly active in treating progressive disease. Levamisole offers a case in point. In 34 animal tumor models in which it was used as a monotherapy no effect was observed; however, following cytoreductive therapy it was active in 13 of 21 systems. The experience in human cancer generally parallels these results. If one accepts the contention that levamisole is the only agent whose animal experience correlates with the human then logically the models in which it has been effective are the most appropriate for considering related agents. One of th difficulties in this consideration is that very little is known about the detailed antitumor mechanisms of the action of levamisole in either the animal models or in human cancer.