Synergistic antitumor activity of cyclophosphamide and ABPP in the treatment of established and advanced tumors in murine tumor models.

Abstract

We have previously shown that the in vivo administration of ABPP, an interferon inducing pyrimidinone, generates activated killer cells that can lyse fresh tumor cells in vitro in 4-h 51chromium release assays. The administration of this agent however has no effect on established tumor. In this communication we show that ABPP, when used in combination with low or moderate doses of cyclophosphamide, can be quite effective against early established (day 3) tumor as well as against advanced, grossly visible (day 8-10) tumor in both the i.p. and pulmonary metastasis model. The synergistic antitumor activity of this chemoimmunotherapeutic regimen was very strong against immunogenic tumors but rather weak against nonimmunogenic tumors. Two treatment cycles were significantly more effective than one and multiple cycles even cured the majority of mice with established i.p. tumor. These experiments demonstrate the potential of chemoimmunotherapeutic regimens and highlight the efficacy of multiple treatment cycles.