Streptococcal preparation OK-432 enhances the antitumor activity of CPT-11 by increasing Th1-cytokine production in mice.
BACKGROUND
The streptococcal preparation OK-432 is an immunomodulator widely used for cancer therapy in Japan. The purpose of this study was to evaluate the efficacy of the combined treatment of OK-432 and CPT-11.


METHODS
In C57BL/6 mice inoculated with B16 melanoma, the antitumor mechanism of this combined therapy was investigated through an analysis of cytokine production by the splenocytes.


RESULTS
SN-38, the active metabolite of CPT-11, exerted dose-dependent inhibition of interferon (IFN)-gamma production induced by OK-432 in mouse splenocytes. In contrast, the optimum concentration of SN-38 increased interleukin (IL)-6 and IL-12 production by OK-432-activated splenocytes. In tumor-bearing mice, CPT-11 inhibited tumor growth and OK-432 had an additive antitumor effect with CPT-11. Investigation of cytokine production showed that CPT-11 treatment principally inhibited IL-12 and IFN-gamma production, which was improved by the combined administration with OK-432.


CONCLUSIONS
These results indicate that CPT-11 inhibits type-1 T helper (Th1) cells despite its potential to stimulate macrophages and that OK-432 enhances the antitumor activity of CPT-11 by increasing Th1-cytokine production.
Wang
X
X
Division of Surgical Oncology, Cancer Research Institute, Kanazawa University, Japan.
Fujimoto
T
T
Zhang
B
B
Mai
M
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D000077146:Irinotecan; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010844:Picibanil / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D018664:Interleukin-12; D010844:Picibanil; D000077146:Irinotecan; D007371:Interferon-gamma; D002166:Camptothecin