Effect of indomethacin on tumorigenicity and immunity induction in a murine model of mammary carcinoma.
Indomethacin, an inhibitor of cyclo-oxygenase given orally, reduced the tumorigenicity of cancer cells in a non-immunogenic murine model of mammary adenocarcinoma (4T1). In the presence of indomethacin, a dose-dependent immune protection could be induced most effectively by immunizing mice with 1 to 3 doses of irradiated tumor cells inoculated at intervals of 7 days prior to challenge with a tumorigenic cell dose. Three immunizations given without indomethacin resulted in tumor growth in 88% of the recipients, and indomethacin treatment started 28 days prior to the challenge dose and given without immunizations led to tumor onset in 83% of mice. In contrast, tumor was documented only in 12% of mice vaccinated with 3 immunization doses and given concomitantly indomethacin. Moreover, 53% of disease-free survivors resisted a second challenge with a high tumorigenic dose. Induction of an anti-tumor immunity in indomethacin-treated mice was further studied as a therapy for tumor-bearing mice. Complete cure was induced in 50% of mice, and a significant reduction in tumor size as well as prolonged survival time were observed in the remaining animals. Immunostimulation by tumor cell vaccination given in the presence of a tolerable dose of indomethacin, therefore, may be incorporated into immunotherapy protocols to activate an anti-tumor response against residual tumor cells that escaped surgery and/or high-dose chemo/radiotherapy.
Morecki
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Department of Bone Marrow Transplantation and Cancer Immunobiology Research Laboratory, Hadassah University Hospital, Jerusalem, Israel.
Yacovlev
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Slavin
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D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016019:Survival Analysis
D019496:Cancer Vaccines; D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin