title: [Anti-tumor immunity induced by OK-432-derived DNA].
abstract: We have tried to identify the effective components of OK-432, a Streptococcus-derived anti-cancer immunotherapeutic agent. In the current study, we investigated the effect of OK-432-derived DNA (OK-DNA) in augmenting anti-cancer immune response. Analysis of OK-DNA with the restriction enzymes Hpa II and Msp I revealed that OK-DNA contained unmethylated CpG motifs. OK-DNA induced Th1-type cytokines, such as IFN-gamma and IL-12, and augmented killer cell activities in vitro on human peripheral blood mononuclear cells, whereas the methylated OK-DNA did not. Cytokines were also produced by OK-DNA-stimulated splenocytes derived from wild-type mice but not from TLR9-deficient mice. In the in vivo study, a peritumoral administration of OK-DNA resulted in a significant inhibition of tumor growth in syngeneic tumor-bearing wild-type and TLR4-deficient mice but not in TLR9-deficient mice. Anti-tumor effect of OK-432 in TLR9-deficient mice was significantly but partially reduced as compared with that in wild-type mice, while the effect of OK-432 was almost completely eliminated in TLR4-deficient mice. These findings suggest that unmethylated CpG-DNA in OK-432 functions as an active component in OK-432-induced anti-cancer immunity via TLR9, at least in part.
authors.affiliation: Second Dept. of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshikawa
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Sharif Uddin
authors.initials: SU
authors.lastname: Ahmed
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tano
authors.forename: Akiko
authors.initials: A
authors.lastname: Sasai
authors.forename: Shin
authors.initials: S
authors.lastname: Kan
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D010844:Picibanil / Q000032:analysis* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D051217:Toll-Like Receptor 9 / Q000502:physiology
chemical_list: D004269:DNA, Bacterial; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D010844:Picibanil; D007371:Interferon-gamma