Anticancer drugs plus cytokines: immunodulation based therapies of mouse tumors

As demonstrated in this laboratory, several cytotoxic anticancer agents hav e immunomodulating effects at relatively low doses and, in combination with non-toxic doses of certain cytokines, can exert immunity-dependent curativ e effects in mouse tumor models. Thus, adriamycin (Dox) has been shown to e nhance the activation of macrophages with associated increases of IL1 and T NF production, to stimulate the production of IL2 and the development and a ction of CTLs. In the EIA lymphoma C57BL/6 mouse model, combinations of app ropriate regimens of Dox plus IL2 or TNF induce cures and the long-term sur vivors exhibit life-long immunological memory. Combinations of cyclophospha mide plus TNF have analogous effects. In the E0771 breast tumor C57BL/6 mou se model, Dox plus TNF at doses which are without antitumor activity when g iven alone, cause complete cures of established tumors with concomitant sti mulation of CTL and NK cells responses. The mechanisms involved in these th erapeutic responses are discussed. In conclusion, the results obtained subs tantiate the possibility of establishing antitumor curative combination reg imens based on the utilization of low non-toxic immunomodulating doses of c ertain anticancer drugs and specific cytokines. (C) 2000 International Soci ety for Immunopharmacology. Published by Elsevier Science Ltd. All rights r eserved.