Enhanced antitumor effect of combination therapy with interleukin-2 and polyribonucleotides against adenocarcinoma 755.
Human recombinant interleukin-2 (IL-2) and interferon (IFN) inducers in combination were evaluated for their in vivo antitumor efficacy in relation to s.c.-implanted adenocarcinoma 755 in C57BL/6 mice. Two IFN inducers, polyinosinic-polycytidylic acid [poly(I)poly(C)] and polyadenylic-polyuridylic acid [poly(A)poly(U)], induced high IFN production in various tissues for a long time compared to treatment with murine interferon-beta. Especially, poly(I)poly(C) at 5 mg/kg, the maximum tolerated dose, produced the highest level of IFN in the tumor, but the tumor did not show regression. Poly(I)poly(C), however, brought about marked regression of the tumor when administered together with IL-2. This combination resulted in cure of some mice when both drugs were administered intraperitoneally. Intraperitoneal injection of IL-2 in combination with poly(I)poly(C) was more effective than intravenous injection of IL-2. The combination of IL-2 and poly(A)poly(U) also showed an enhanced antitumor effect. Thus, endogenous IFN produced by IFN inducers as well as exogenous IFN as reported previously potentiated the antitumor effect when administered together with IL-2. The degree of potentiation by combination of IL-2 and IFN inducers may depend on the level of IL-2 and IFN at the injection site.
Iigo
M
M
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Nakajima
Y
Y
Nishikata
K
K
Hoshi
A
A
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004357:Drug Synergism; D007370:Interferon Type I / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011063:Poly A-U / Q000008:administration & dosage* / Q000494:pharmacology; D011070:Poly I-C / Q000008:administration & dosage* / Q000494:pharmacology; D014018:Tissue Distribution
D007370:Interferon Type I; D007376:Interleukin-2; D011063:Poly A-U; D011070:Poly I-C