Streptococcal preparation OK-432

A new maturation factor of monocyte-derived dendritic cells for clinical use

Hideo Kuroki, Takashi Morisaki, Kotaro Matsumoto, Hideya Ohnishi, Eishi Baba, Masao Tanaka, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

49 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)561-568
ページ数8
ジャーナルCancer Immunology, Immunotherapy
52
発行部数9
DOI
出版物ステータス出版済み - 9 1 2003

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Picibanil
Dendritic Cells
Monocytes
Interleukin-12
Lipopolysaccharides
T-Lymphocytes
Dinoprostone
Tumor Necrosis Factor-alpha
Active Immunotherapy
Cytochalasin B
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Neutralizing Antibodies
Interleukin-4
Immunotherapy
Interferons

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

これを引用

Streptococcal preparation OK-432 : A new maturation factor of monocyte-derived dendritic cells for clinical use. / Kuroki, Hideo; Morisaki, Takashi; Matsumoto, Kotaro; Ohnishi, Hideya; Baba, Eishi; Tanaka, Masao; Katano, Mitsuo.

:: Cancer Immunology, Immunotherapy, 巻 52, 番号 9, 01.09.2003, p. 561-568.

研究成果: ジャーナルへの寄稿記事

Kuroki, Hideo ; Morisaki, Takashi ; Matsumoto, Kotaro ; Ohnishi, Hideya ; Baba, Eishi ; Tanaka, Masao ; Katano, Mitsuo. / Streptococcal preparation OK-432 : A new maturation factor of monocyte-derived dendritic cells for clinical use. :: Cancer Immunology, Immunotherapy. 2003 ; 巻 52, 番号 9. pp. 561-568.
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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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AU - Baba, Eishi

AU - Tanaka, Masao

AU - Katano, Mitsuo

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