Relative contribution of antiproliferative and host immunity-associated activity of mouse interferon in murine tumor therapy.
Administration of mouse interferon (IFN; 0.5 to 1 X 10(7) reference units/mg protein) inhibited the growth of Meth A and Meth 1 fibrosarcomas, but to a lesser extent, if at all, the growth of Colon 26 adenocarcinoma in BALB/c mice. The in vitro IFN sensitivity of these three tumors was not consistent with the in vivo therapeutic response in mice bearing these tumors under the present experimental conditions; Colon 26, the most sensitive of the three tumors in the in vitro antiproliferation test, did not respond or responded most poorly to IFN therapy; furthermore, Meth A and Meth 1 tumors responded similarly well to IFN therapy, although there was about a 100-fold difference in their in vitro IFN sensitivity. These results as well as the kinetic analysis of IFN concentrations of the serum of Meth A- or Colon 26-bearing mice did not indicate that the antiproliferative activity of IFN was solely responsible for its in vivo therapeutic effect. In contrast, abrogation of T-cell immunity by alpha mouse thymocyte globulin completely nullified the IFN-dependent therapeutic effect in Meth A-bearing mice. Furthermore, the IFN-dependent therapeutic response in Meth A tumors was much weaker in T-cell-defective BALB/c (nu/nu) mice than that in immunologically competent BALB/c (+/+) mice and was marginal, if present at all, confirming that T-cell immunity was involved in the IFN-dependent therapeutic effect and suggesting that the antiproliferative activity of IFN may only be responsible to a small extent for the therapeutic effect.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013045:Species Specificity
D007370:Interferon Type I