Combined immunotherapy with macrophage colony-stimulating factor and OK-432 prevents peritoneal metastasis in mice

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Peritoneal metastasis after surgery is a critical prognostic factor in cancer patients. This type of recurrence is considered to originate from microscopic dissemination in the peritoneal cavity, and the eradication of such dissemination is necessary for the improvement of survival. We evaluated the preventive effect of intraperitoneal administration of macrophage colony-stimulating factor (M-CSF) and OK-432 on the development of peritoneal metastasis.Intraperitoneal administration of M-CSF (1×104U) and OK-432 (0.2KE) for 5 days significantly increased the number of peritoneal effusion cells and peritoneal macrophages as well as the cytotoxicity of the peritoneal macrophages when compared with M-CSF or OK-432 alone. In addition, the release of TNF-α and NO2- from macrophages was significantly increased by combined intraperitoneal administration of M-CSF and OK-432.In a peritoneal metastasis model created by peritoneal inoculation of colon 26 cells into BALB/c mice (male, 6 weeks old), the combined intraperitoneal administration of M-CSF and OK-432 inhibited weight loss, reduced the intraperitoneal tumor weight, and prolonged the survival of mice as compared with M-CSF or OK-432 alone.In conclusion, combined intraperitoneal immunotherapy with M-CSF and OK-432 may be useful for the treatment or prevention of peritoneal metastasis.
日本癌病態治療研究会の論文