TY - JOUR
T1 - Streptococcal preparation OK-432
T2 - A new maturation factor of monocyte-derived dendritic cells for clinical use
AU - Kuroki, Hideo
AU - Morisaki, Takashi
AU - Matsumoto, Kotaro
AU - Onishi, Hideya
AU - Baba, Eishi
AU - Tanaka, Masao
AU - Katano, Mitsuo
N1 - Funding Information:
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 Technol- ogy of Japan. We thank Takaaki Kanemaru and Kaori Nomiyama for their technical assistance.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0042856241&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042856241&partnerID=8YFLogxK
U2 - 10.1007/s00262-003-0394-7
DO - 10.1007/s00262-003-0394-7
M3 - Article
C2 - 14627128
AN - SCOPUS:0042856241
SN - 0340-7004
VL - 52
SP - 561
EP - 568
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 9
ER -
