Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning.
OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.
Hashimoto
Masahito
M
Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan.
Takashige
Katsuhiro
K
Furuyashiki
Maiko
M
Yoshidome
Keitaro
K
Sano
Ryoko
R
Kawamura
Yutaka
Y
Ijichi
Shinji
S
Morioka
Hirofumi
H
Koide
Hiroyuki
H
Oku
Naoto
N
Moriya
Yoichiro
Y
Kusumoto
Shoich
S
Suda
Yasuo
Y
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000628:therapy*; D017830:Octoxynol; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols
D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D010844:Picibanil; D011092:Polyethylene Glycols; D017830:Octoxynol; C010615:Nonidet P-40