Chemoimmunotherapy of L1210 leukemia with adriamycin, cyclophosphamide, and OK-432, and their effects on the generation of antitumor immunity.
The synergistic effects of combined chemotherapy with adriamycin (ADR) and cyclophosphamide (CY) on L1210 tumors in mice were potentiated by use of a streptococcal preparation, OK-432, in a time- and dose-dependent way. Some mice were cured by treatment with the three agents, and resisted a later challenge by L1210 but not P388 leukemia cells. This immunity was blocked by administration of antimacrophage agents or CY. The effects of OK-432 were also studied with mice sensitized by L1210 cells attenuated with mitomycin C. OK-432 potentiated syngeneic and semi-syngeneic transplantation resistance in vivo and augmented primary and secondary cytotoxicity mediated by spleen cells in vitro. In vivo administration of ADR and CY together enhanced in vivo tumor transplantation resistance and in vitro cytotoxicity was blocked, but this inhibition was reversed by injection of OK-432. The results suggested that OK-432 acted by increasing the activity of cytotoxic spleen cells against L1210 cells, which are fast-growing and poorly immunogenic, and that this cytotoxicity killed tumor cells that survived the chemotherapy.
D000818:Animals; D001688:Biological Products / Q000627:therapeutic use*; D002351:Carrageenan / Q000494:pharmacology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D007108:Immune Tolerance / Q000187:drug effects*; D007167:Immunotherapy; D007939:Leukemia L1210 / Q000188:drug therapy / Q000628:therapy*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D010844:Picibanil / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014343:Trypan Blue / Q000494:pharmacology
D001688:Biological Products; D010844:Picibanil; D004317:Doxorubicin; D003520:Cyclophosphamide; D002351:Carrageenan; D014343:Trypan Blue