TUMORICIDAL EFFECT OF HUMAN MACROPHAGE-COLONY-STIMULATING FACTOR AGAINST HUMAN-OVARIAN-CARCINOMA-BEARING ATHYMIC MICE AND ITS THERAPEUTIC EFFECT WHEN COMBINED WITH CISPLATIN

The effect of human macrophage-colony-stimulating factor (hM-CSF) on t umoricidal activity was examined in athymic mice bearing the human ova rian cancer cell line, HRA, injected intraperitoneally (i.p.). The sur vival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P <0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly d ecreased in the hM-CSF-treated groups, and macrophages phagocytosed tu mor cells, indicating a contact-mediated direct cytolysis. The combine d therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic m ice were also studied. The mean survival period was 25.4, 47.2, 42.4 a nd 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cis platin and hM-CSF. The survival period and rate were significantly lon ger (P <0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the t herapeutic effectiveness of the combined use. Moreover, hM-CSF is effe ctive against granulocytopenia due to bone marrow suppression caused b y cisplatin. Our data demonstrate that hM-CSF administered i. p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i. p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic e ffect.