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Streptococcal preparation OK-432: a new maturation factor of monocyte-derived dendritic cells for clinical use

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Abstract

For vaccinations based on dendritic cells (DCs), maturation of DCs is critical to the induction of T-cell responses. We tested the efficacy of streptococcal preparation OK-432 as a Good Manufacturing Practice (GMP)–grade maturation agent. OK-432 is currently used in Japan as a cancer immunotherapy drug. Immature monocyte-derived dendritic cells (imMo-DCs) isolated from human peripheral blood monocytes stimulated with granulocyte-macrophage colony stimulating factor and interleukin-4 were exposed to maturation factors, i.e., lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) plus prostaglandin E2 (PGE2), and OK-432 for 2 days. OK-432 increased expression of activation- and maturation-related molecules such as HLA-DR, CD80, CD83, and CD86 in imMo-DCs at levels similar to that of TNF-α plus PGE2, and higher than that of LPS. All agents examined induced allogeneic T-cell proliferation at a similar level. Only OK-432 caused significant production of interleukin-12 (IL-12) p70 and interferon γ (IFN-γ) at both the mRNA and protein levels in imMo-DCs. Neutralizing antibody against IL-12 p70 blocked IFN-γ secretion from OK-432–stimulated Mo-DCs. IL-12 p70 produced by OK-432–stimulated imMo-DCs induced secretion of IFN-γ by CD4+ T cells. OK-432 and LPS activated nuclear factor κ B (NF-κB) in imMo-DCs. Both secretion of IL-12 p70 and IFN-γ and activation of NF-κB induced by OK-432 were suppressed when imMo-DCs were pretreated with cytochalasin B. These results indicate that uptake of OK-432 by imMo-DCs is an early critical event for IL-12 p70 production and that NF-κB activation induced by OK-432 also contributes partially to IL-12 p70 production. In conclusion, OK-432 is a GMP-grade maturation agent and may be a potential tool for DC-based vaccine therapies.

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Acknowledgements

OK-432 was kindly provided by Chugai Pharmaceutical, Tokyo, Japan. This study was supported in part by a Grant-in-Aid for General Scientific Researches (12557106) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Takaaki Kanemaru and Kaori Nomiyama for their technical assistance.

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Authors and Affiliations

  1. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Hideo Kuroki, Takashi Morisaki, Kotaro Matsumoto, Hideya Onishi, Eishi Baba & Mitsuo Katano

  2. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masao Tanaka

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  1. Hideo Kuroki
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  2. Takashi Morisaki
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Correspondence to Mitsuo Katano.

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Kuroki, H., Morisaki, T., Matsumoto, K. et al. Streptococcal preparation OK-432: a new maturation factor of monocyte-derived dendritic cells for clinical use. Cancer Immunol Immunother 52, 561–568 (2003). https://doi.org/10.1007/s00262-003-0394-7

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