Stimulation of non-specific resistance to tumors in the mouse using a poly(maleic-acid-styrene)-conjugated neocarzinostatin.
The development of non-specific resistance to tumors following stimulation with poly(maleic-acid-styrene)-conjugated neocarzinostatin (SMANCS), a polymer-conjugated derivative of neocarzinostatin, was investigated in mice. The growth of syngeneic solid tumors (Meth-A fibrosarcoma and RL male 1 leukemia) inoculated into BALB/c mice was suppressed after one treatment with SMANCS at doses ranging from 0.14 mg/kg to 3.4 mg/kg i.v. 24 h before tumor implantation. Since previously observations concerning SMANCS have shown that it disappeared within 1.5 h after i.v. administration in mice and that it was inactivated quickly in plasma, SMANCS evidently inhibited tumor growth by mediating non-specific resistance. In addition, the non-specific resistance to tumors stimulated by SMANCS could be passively transferred to untreated mice by serum which was shown to contain interferon (IFN) from 12 h to 20 h after SMANCS administration. However, the resistance was not produced by serum prepared from mice at 8 h or 32 h after administration presumably because of the observation that the interferon activity was only demonstrated from 12 h to 28 h after SMANCS stimulation. When the serum specimens were treated with anti-IFN-gamma antiserum, the antitumor activity of the sera was abrogated. However, no significant change was detected in the antitumor activity of the specimens following treatment with anti-IFN-alpha/beta antiserum. Treatment of mice with SMANCS and anti-IFN-gamma antiserum together resulted in the elimination of the non-specific resistance to tumors. The IFN induced in the sera of mice by SMANCS was shown to be 57% IFN-gamma and 41% IFN-alpha/beta. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-gamma, and treatment of SMANCS-stimulated mice with both anti-IFN-gamma and anti-IFN-alpha/beta antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-gamma and IFN-alpha/beta production, in this case, it is only the former which mediates the non-specific resistance to tumors.
Suzuki
F
F
Department of Microbiology, Kumamoto University School of Medicine, Japan.
Pollard
R B
RB
Maeda
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D005260:Female; D005663:Furans / Q000494:pharmacology*; D007106:Immune Sera / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D007372:Interferons / Q000276:immunology / Q000502:physiology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008299:Maleic Anhydrides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology*; D011137:Polystyrenes / Q000494:pharmacology*; D009353:Zinostatin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D005663:Furans; D007106:Immune Sera; D008298:Maleates; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; C059316:poly(styrene-co-maleic acid)butyl ester; D007372:Interferons; D009353:Zinostatin