Evidence of a role for NK cells in oxazaphosphorine-mediated tumor regression.
The present studies showed that nude mice xenotransplanted with L5222 leukemia responded as did syngeneic BD IX rats to low doses of mafosfamide or cyclophosphamide. Unlike rats, nude mice rarely showed resistance to a second tumor challenge. The observation that concurrent treatment of rats with cyclosporin A did not alter the rate of survival clearly indicated a T-cell-independent mechanism of tumor defense. The incidence of lung colonies from i.v. injected Lewis lung-tumor cells could be enhanced by a high dose pretreatment with mafosfamide or cyclophosphamide, whereas pretreatment at low doses was inhibitory. Since identical experiments carried out in NK-cell-deficient C57Bl/6 "beige" mice did not show such an effect, NK cells appeared to represent a possible effector cell in oxazaphosphorine-mediated antitumor effects. This assumption was further supported by the fact that enhanced NK cell activity could be observed in the 51Cr release assay using spleen cells from mafosfamide-treated L5222-bearing rats. The transplantation of the unrelated syngeneic ovarian carcinoma OV-342 to animals that had previously been cured of L5222 leukemia did not lead to the rejection of this tumor. This indicates that a specific resistance against L5222 leukemia had developed. In contrast, a T-cell-dependent antitumor effect was demonstrated for mafosfamide in the MOPC-315 mouse plasmocytoma. Therefore, we conclude that the effector cell for tumor rejection depends on the type of tumor. This, of course, does not exclude a common target cell for the immunopharmacological activity of oxazaphosphorines.
Reissmann
T
T
ASTA Pharma AG, Department of Experimental Cancer Research, Bielefeld, Federal Republic of Germany.
Hilgard
P
P
Voegeli
R
R
Zeller
J
J
D000818:Animals; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003524:Cyclosporins / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology*; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010954:Plasmacytoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured
D003524:Cyclosporins; C048341:mafosfamide; D003520:Cyclophosphamide