Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent

Journal of Immunotherapy
Tetsuya OshikawaMitsunobu Sato

Abstract

OK-432 is a Streptococcus-derived immunotherapeutic agent for malignancies. Our group has tried to identify the effective components of OK-432 and has succeeded in isolating a lipoteichoic acid-related preparation designated as OK-PSA, which is a strong inducer of T helper 1 (T(H)1) cells, and elicits an anticancer effect via Toll-like receptor (TLR) 4. Conversely, bacterial DNA with unmethylated CpG motifs can stimulate a T(H)1-type host response via TLR9. The unmethylated CpG DNA contained in OK-432 may play a role in its anticancer effect. In the current study, we investigated the effect of OK-432-derived DNA (OK-DNA) in augmenting the anticancer immune response. Analysis of OK-DNA with the restriction enzymes Hpa II and MspI revealed that OK-DNA contained unmethylated CpG motifs. OK-DNA induced TH1-type cytokines such as interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-12, and IL-18 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, peritumoral administration of OK-DNA resulted in a signi...Continue Reading

References

Feb 1, 1979·International Journal of Cancer. Journal International Du Cancer·L C AnderssonC G Gahmberg
Dec 1, 1967·Japanese Journal of Microbiology·H OkamotoR Shimizu
Jan 1, 1983·Annual Review of Biochemistry·W Doerfler
Jan 1, 1993·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·F KikkawaK Kuzuya
May 4, 1993·Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy·M OkamotoM Sato
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·F L RockJ F Bazan
Apr 10, 1999·The Journal of Biological Chemistry·J C ChowF Gusovsky
Jun 8, 1999·The Journal of Experimental Medicine·R ShimazuM Kimoto
Jul 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G B LipfordH Wagner
Aug 30, 2000·Nature·A Aderem, R J Ulevitch
Dec 29, 2000·Nature·H HemmiS Akira
Feb 28, 2002·Annual Review of Immunology·Arthur M Krieg
Apr 2, 2003·Cancer Immunology, Immunotherapy : CII·Tsuyoshi ItohHisakazu Yamagishi
Nov 25, 2003·Cancer Immunology, Immunotherapy : CII·Hideo KurokiMitsuo Katano

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Citations

Aug 29, 2009·The Journal of Infectious Diseases·Guadalupe Cortés, Michael R Wessels
Dec 4, 2013·Immunology and Cell Biology·Ke PanJian-chuan Xia
Feb 9, 2016·World Journal of Gastrointestinal Pharmacology and Therapeutics·Masato OkamotoSadamu Homma
Feb 26, 2013·European Journal of Immunology·Michiko HirayamaHiroshi Shiku
Apr 2, 2020·Pharmaceutics·Terutsugu KoyaShigetaka Shimodaira
Mar 22, 2014·Molecular and Clinical Oncology·Yuta ShibamotoHidenori Takahashi
Sep 3, 2008·Molecular Biology Reports·Yan-Bei ZhangRong-Yu Liu
Mar 24, 2021·Cancer Gene Therapy·Zeynab MarzhoseyniHamed Mirzaei
Dec 11, 2007·International Immunopharmacology·Masahito HashimotoYasuo Suda

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