Peri-tumor interleukin-2 causes systemic therapeutic effect via interferon-gamma induction.
This study compares the direct local therapeutic effects of multiple peri-tumor injections of interleukin-2 (IL-2) and interferon gamma (IFN-gamma), also the associated systemic therapeutic effects on distant untreated tumors resulting from the peritumor injections. The therapeutic effects were tested against intramammary implants of an immunogenic, syngeneic C3H mammary carcinoma. Peritumor IL-2 and IFN-gamma had nearly equal local and systemic therapeutic effects. In a comparison of the therapeutic effects of IL-2 and IFN-gamma injected systemically, only the IFN-gamma injections resulted in a significant number of cures. IL-2 and IFN-gamma did not have an additive effect when used in combination, suggesting that they have connected, rather than separate, paths of action in the anti-tumor immune response. The injection of anti-IFN-gamma-MAb abrogated the systemic therapeutic effect of peri-tumor IL-2, indicating that the systemic therapeutic effect was the result of IFN-gamma induction at the IL-2 injection site.
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263-0001.
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D000818:Animals; D000911:Antibodies, Monoclonal; D005260:Female; D007267:Injections; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma