title: Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation, by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of OK-432: comparison between the TS-2-binding and TS-2-unbinding fraction.
abstract: We have previously isolated a lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal agent, by affinity chromatography on a CNBr-activated Sepharose 4B bound TS-2 monoclonal antibody (mAb) that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. In the current study, we compared the cytokine-inducing and anti-tumor activities of OK-PSA, a TS-2-binding fraction, with those of OK-PTF, a TS-2-unbinding fraction, in order to determine the efficacy of OK-PSA for clinical use in affinity chromatography using TS-2. In the in vitro experiments using human peripheral blood mononuclear cells (PBMCs), OK-PSA markedly induced Th1-type cytokines, while interleukin (IL)-6 and IL-10, Th2-type cytokines, were induced by OK-PTF. Th1-cytokine induction by OK-PTF was not dose-dependent and was suppressed when PBMCs were treated with a high concentration of OK-PTF. In a mouse model, Th1 cytokines were also induced by OK-PSA and Th2 cytokines were induced by OK-PTF. Th2 cytokine-inducing activity of OK-PTF was accelerated in tumor-bearing mice relative to that in healthy mice. Although the anti-tumor effect of OK-PTF was statistically significant, it was much weaker than that of OK-PSA. A significant difference between the anti-tumor effect of OK-PSA and that of OK-PTF was observed (P<0.05). Finally, OK-PSA elicited its cytokine-inducing effect via Toll-like receptor (TLR) 4, whereas OK-PTF-induced signaling was mediated by both TLR2 and TLR4. These findings strongly suggested that the affinity chromatography using TS-2 is a useful strategy to separate the effective component for cancer therapy (OK-PSA) from other components.
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 7708504, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshikawa
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Go
authors.initials: G
authors.lastname: Ohe
authors.forename: Sachiko
authors.initials: S
authors.lastname: Furuichi
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Sharif
authors.initials: S
authors.lastname: Uddin Ahmed
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Moriya
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsubara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ryoma
authors.forename: Motoo
authors.initials: M
authors.lastname: Saito
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006825:Hybridomas; D066298:In Vitro Techniques; D007369:Interferon Inducers / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008156:Luciferases / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010844:Picibanil / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D003470:Culture Media; D016207:Cytokines; D007369:Interferon Inducers; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D010844:Picibanil; D007371:Interferon-gamma; D008156:Luciferases