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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1985-09, Vol.45 (9), p.4215-4218
Main Authors: BEREK, J. S, LICHTENSTEIN, A. K, KNOX, R. M, JUNG, T. S, ROSE, T. P, CANTRELL, J. L, ZIGHELBOIM, J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Disease Models, Animal
Endotoxins - therapeutic use
Female
Female genital diseases
Gynecology. Andrology. Obstetrics
Immunotherapy - methods
Medical sciences
Mice
Mice, Inbred C3H
Neutrophils - immunology
Ovarian Neoplasms - therapy
Propionibacterium acnes
Salmonella - pathogenicity
Tumors
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Summary: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.
ISSN:0008-5472