[Effects of IgG-Fc-mitomycin C conjugate on cancer cells].
The binding of IgF Fc was studied in cultured tumor cells and antitumor effects of Fc-mitomycin C conjugate (Fc-MMC) on cultured tumor cells and tumor bearing mice were examined. 125I-labeled Fc bound to tumor cells Colon26, HLE, MKN28 and MKN74, and its binding was inhibited by the addition of non-labeled Fc. The binding increased in the course of exposure time up to 60 minutes and reached a value of more than 90% within 30 minutes. The cytotoxicity to the cultured tumor cells were not different in the 60 minutes incubation, but in the 30 minutes incubation, Fc-MMC showed more than two times as strong cytotoxicity as MMC (p<0.005). 2.5 mg/kg of MMC and 2.5 mg/kg of Fc-MMC equivalent to free MMC concentration were administered to Colon26 bearing BALB/c mice. The tumor growth in Fc-MMC-administered mice was lower than that in MMC-administered mice. 1.25 mg/kg and 2.5 mg/kg of agents were given to P-388 bearing mice, and the survival time in 1.25 mg/kg of Fc-MMC-administered mice was significantly longer than that in MMC-administered mice (p < 0.005). The body weight was reduced in MMC 2.5 mg/kg administered mice, but these reduction was not observed in Fc-MMC group. These observation suggest that Fc-MMC may be a promising anticancer agent on clinical applications.
Baba
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First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D011961:Receptors, Fc / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D000922:Immunotoxins; D011961:Receptors, Fc; D016685:Mitomycin