Importance of coordinated immune stimulation in experimental antitumor treatment.

We have proposed an antitumor therapeutic model in mice grafted with Crocker 180TG cells. The treatment strategy involves a coordinated immune stimulation which should always precede treatment of target cells. Potent stimulators mobilizing the majority of immune competent cells can be injected only once since repetition results in adverse effects on the response. Thus, to circumvent this difficulty, we propose the amplification, after a single shot of Corynebacterium parvum extract, of the immune response by cimetidine. Indeed, it has been reported that cimetidine inhibits suppressor T cell functions. The second phase acting on the target employs interferon and arginine butyrate since they reconvert a number of transformed target cells to normal phenotype. Important antitumor effects can be obtained in the present model even if the treatment is initiated relatively late after tumor graft. All the drugs employed are harmless on normal cells and are used at relatively low concentrations.