Eradication of disseminated murine leukemia by treatment with high-dose interleukin 2.
Interleukin 2 (IL 2) in high concentration induces lymphocytes to become nonspecifically cytolytic to a wide variety of tumor targets. We evaluated the therapeutic potential of such lymphokine-activated killer (LAK) cells in vivo and high-dose II 2 in vivo against disseminated murine leukemia. To quantitate the potential anti-leukemia effect of LAK cells in vivo, B6 mice were injected i.p. with graded doses of FBL-3 leukemia cells followed by LAK cells. In this Winn-type assay, 1 X 10(7) LAK cells were able to prevent the outgrowth of 1 X 10(2) FBL-3 cells in only 50% of mice and did not prevent the outgrowth of 1 X 10(6) tumor cells. Thus LAK cells, highly cytolytic to FBL-3 in vitro, mediated only a limited anti-tumor effect when applied directly to leukemia cells in vivo. LAK cells used as an adjunct to chemotherapy induced a small but non-curative effect against FBL-3, however. In this circumstance, LAK cells were markedly less effective than were immune spleen cells from mice previously sensitized to FBL-3. To test the anti-leukemia effect of high-dose IL 2 in vivo, B6 mice were inoculated with 5 X 10(6) FBL-3 cells followed by repeated doses of IL 2 at dose levels shown to induce LAK in vivo. "LAK-inducing" IL 2 doses on days 5 to 9 after FBL-3 inoculation, when tumor was disseminated, cured 50% of the mice. Treatment on days 5 to 9 was far more effective than on days 0 to 4, implying that the evolution of a host-tumor interaction was essential for the therapeutic effect of IL 2. Mice cured of FBL-3 by high-dose IL 2 were found to be immune to FBL-3, suggesting that tumor eradication resulted from a collaboration between LAK activity and tumor-specific immunity.
D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005622:Friend murine leukemia virus; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000628:therapy; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
D007376:Interleukin-2; D003520:Cyclophosphamide