In vivo characterization of immunogenicity of a mitoxantrone-resistant murine P388 leukemia.
The Mitoxantrone-resistant murine leukemia P388/Mitox, expressing the multidrug-resistant phenotype, has a higher immunogenicity than the parent sensitive P388. This could be shown in vivo by immunization with lethally-irradiated tumor cells. If the P388/Mitox was used for immunization before subsequent challenge with viable tumor cells of the same line, this resulted in a partial rejection of tumors and production of a substantial number of tumor-free survivors. For an effective immunization at least two primings s.c., i.v. or i.p. with at least 10(6) irradiated cells were necessary. This protected the recipient mice from a challenge of up to 10(8) viable cells over a period of at least 75 days. Treatment of BDF1 mice with the T-cell suppressor Cyclosporin A prevents immunization. In nude mice no immunization effect could be obtained. It was possible to transfer immunity adoptively with spleen cells from mice, which were treated with irradiated tumor cells of the P388/Mitox line. Treatment of tumor-bearing mice with IL-2 resulted in a prolongation of survival both when it was administered prophylactically before transplantation of P388/Mitox and at an advanced stage (day 7-11). Also the alkyl-phosphocholine hexadecylphosphocholine was significantly effective in the resistant but not in the parent P388 leukemia. The data presented demonstrate that by development of a multidrug-resistance, concomitantly a xenogenization must have taken place which leads to a recognition of cells by immune mechanisms. In our model, T-lymphocytes and NK-/LAK-cells probably play a role in the immunologically conditioned rejection of tumor cells of the P388/Mitox leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Max-Delbrück-Centre of Molecular Medicine, Berlin-Buch, Germany.
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Fichtner
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Reipert
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Becker
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Lemm
D000818:Animals; D000917:Antibody Formation; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008942:Mitoxantrone / Q000494:pharmacology*; D010641:Phenotype
D008942:Mitoxantrone