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.