An antigen related to the phenotype of multi-drug resistance can be induced in vivo and used as a target for immunotherapy of rat leukemia.
Several laboratories have reported that new plasma membrane peptides appear in rodent and human cells after induction of in-vitro resistance to vinca alkaloids, anthracyclines and other anti-neoplastic drugs. Recently, murine monoclonal antibodies have been produced that recognize surface components of such drug-resistant cells. The work presented here describes the development of an in-vivo animal model of this phenomenon using a rat myeloid leukemia. Brown Norway rats were made leukemic with promyelocytes of the BNML line and subsequently were treated with 7.7 mg kg-1 of daunorubicin. After eight cycles of passage-treatment-regrowth, the resulting cells reacted with this antibody in immunofluorescence and cytotoxicity assays. Animals injected with cells that had been pre-incubated with antibody in the absence of complement survived significantly longer than did the controls. Further prolongation of survival occurred when the cells were treated with a second antibody of a different specificity. These results demonstrate that some of the changes associated with in-vitro drug resistance occur also in vivo and potentially may be exploited as a focus for immunotherapy.
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D003630:Daunorubicin / Q000627:therapeutic use; D004195:Disease Models, Animal; D004351:Drug Resistance; D005260:Female; D005455:Fluorescent Antibody Technique; D007114:Immunization; D007167:Immunotherapy; D007942:Leukemia, Experimental / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D051381:Rats; D013499:Surface Properties; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D003630:Daunorubicin