Synergistic effects of combination sequential immunotherapies in a murine ovarian cancer model.
The antitumor effects of Corynebacterium parvum in a murine ovarian teratocarcinoma model depend upon a sequential activation of neutrophils and macrophages within the peritoneal cavity. We studied the sequential administration of biological response modifiers that independently activate each phase of the response. Tumor-challenged mice treated by i.p. injection of a pyridine-extracted fraction of cell-free Propionibacterium acnes (PA-PE, 1400 micrograms) demonstrated prolonged survival in less than 20% of the cases. An i.p. injection of a detoxified Salmonella endotoxin (DSE) preparation (150 micrograms) had no effect on tumor outgrowth. However, i.p. treatment with PA-PE (1400 micrograms), followed by 150 micrograms of DSE 1 day later, resulted in long-term survival (greater than 100 days) in 40 to 60% of mice. This antitumor effect was only evident when PA-PE was administered first (before DSE) and optimal when DSE was administered 24 h after PA-PE. The synergistic antitumor effect could be duplicated when tumor-challenged mice were first treated i.p. with peritoneal polymorphonuclear leukocytes, elicited by injection of PA-PE, and then treated with DSE 18 h later. These data indicate that appropriately timed injection of biological response modifiers with complementary effects can result in a synergistic prevention of tumor growth.
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000627:therapeutic use; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000276:immunology; D010051:Ovarian Neoplasms / Q000628:therapy*; D011425:Propionibacterium acnes; D012475:Salmonella / Q000472:pathogenicity
D004731:Endotoxins