Immunogenic potential of tumor cells after treatment with antitumor chemotherapeutic agents.

Mouse EL-4 lymphoma cells exposed in vitro for short periods to 4-hydroperoxycyclophosphamide, an in vitro active derivative of cyclophosphamide, and to another alkylating agent, cis-diamminedichloroplatinum(II), as well as to mitomycin C, induced development of antitumor immunity in syngeneic mice co-administered with OK-432, an immunostimulator prepared from streptococci. The anthracyclines (adriamycin and daunomycin) were very slightly effective. The efficacy of the alkylating agents in inducing tumor immunity was also demonstrated by their ability to stimulate secondary in vitro generation of splenic cytotoxicity. These data supported the proposed explanation for effectiveness of chemoimmunotherapy against poorly immunogenic tumors.