2003 Fiscal Year Annual Research Report

Innate immunityの活性化による抗がん免疫療法

Research Project

Project/Area Number	15025278
Research Institution	Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
Principal Investigator	瀬谷司大阪府立成人病センター研究所, 研究所長 (10301805)
Co-Investigator(Kenkyū-buntansha)	赤澤隆大阪府立成人病センター研究所, 研究員 (80359299)
Keywords	樹状細胞 / Toll-like receptor / ペプチドワクチン療法 / アジュバント / NK / CTL / MyD88 / TICAM-1(TRIF)
Research Abstract	今年度は以下の2点を明らかにし、公表又は投稿中である。1.抗がん免疫成立におけるToll-like receptor (TLR)の役割:抗がんCTLの誘導にMyD88依存性経路の活性化が必須である(Akazawa et al.,2004 Cencer Res.).2.抗がんCTLおよびNKの活性化をoptimunにするにはTICAM-1依存性経路が関与する(投稿予定)。1.についてはヒトTLRの抗体阻害が樹状細胞活性化を抑制すること(Uehori et al.,2003 Infect. Immun.)、BCG刺激((TLR2/4活性化)が82もの遺伝子を特異誘導すること(Begum et al,2004 Infect.Immun.)などからCTL誘導には樹状細胞のTLR刺激が必要なこと、さらにMyD88-/-マウスを用いた移植がんの退縮実験から、BCG等のTLRリガンドがペプチドワクチン依存的な増強に必須なこと、この際MyD88依存系経路CTL誘導に関与することが判明せしめる(Akazawa et al.,2004 Cancer Res.)。2.についてNKとCTLの共役的活性化が抗がん免疫の立上げに重要であること、どちらかのみの活性化ではMHCレベルの高低でセレクションが働くことをしめしてきた(Anticancer Res.,Review)。この点を補う試薬(特に微生物成分)をスクリーニング中である。スピルリナ(Masuda et al.,投稿中)、Potyl:C(Okuda et al.投稿中)などを活性同定しつつある。

Research Products

(23 results)

All Other

All Publications (23 results)

[Publications] Hazeki, K, Seya et al.: "TLR-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and-independent pathways."Eur.J.Immunol. 33. 740-747 (2003)
[Publications] Inoue, N, Seya et al.: "Disruption of the mouse CD46 caused an accelerated spontaneous acrosome reaction in sperm."Molec.Cell.Biol. 23. 2614-2622 (2003)
[Publications] Oshiumi, H., Seya et al.: "A novel adapter molecule that participates in Toll-like receptor-mediated interferon-beta induction"Nature Immunol. 4. 161-167 (2003)
[Publications] Oshiumi, H., Seya et al.: "Prediction of the prototype of the human Toll-like receptor gene family from the Pufferfish Fugu. rubripes genome"Immunogenetics. 54. 791-800 (2003)
[Publications] Takeuchi, J., Seya et al.: "TGF-betal Maintains the Skin Homeostasis by Modulating Responsiveness of Langerhans cells Against Bacteria"Biochem.Biophys.Res.Commun. 306. 674-679 (2003)
[Publications] Uehori, J, Seya et al.: "Simultaneous blocking of human Toll-like receptor 2 and 4 suppresses myeloid dendritic cell maturation induced by Mycobacterium bovis bacillus Calmette-Guerin (BCG)-peptidoglycan (PGN)."Infect. Immun. 71. 4238-4249 (2003)
[Publications] Shingai, M, Seya et al.: "Receptor usage by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis."J.Gen.Virol. 84. 2133-2143 (2003)
[Publications] Matsumoto, M, Seya et al.: "Subcellular localization of human Toll-like receptor 3 in human dendritic cells"J.Immunol. 171. 3154-3162 (2003)
[Publications] Oshiumi, H, Seya et al.: "Identification of the Toll-like receptor (TLR)-adapter that participates in TLR4-mediated interferon-beta induction."J.Biol.Chem. 278. 49751-79762 (2003)
[Publications] Akazawa T., Seya et al.: "Adjuvant-mediated tumor regression and tumor-specific CTL induction are impaired in MyD88-deficient mice"Cancer Res.. 64. 757-764 (2003)
[Publications] Tanabe, M, Seya et al.: "Up-regulation of a receptor for dsRNA, Toll-like receptor 3, in human myeloid dendritic cells via measles virus infection"Biochem.Biophys.Res.Commun. 311. 39-48 (2003)
[Publications] Honda, K, Seya et al.: "Selective contribution of IFN-a/b signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection"Proc.Natl.Acad.Sci.USA. 100. 10872-10877 (2003)
[Publications] Begum, N.A Seya et al.: "Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA subtraction in Human Macrophages"Infect.Immun. 72. 937-948 (2003)
[Publications] Matsumoto M., Seya et al.: "Minireview Toll-like receptor3 : A Link between Toll-like reeptor, Intereferon and Virus"Microbiol.Immunol.. 48(3). 147-154 (2004)
[Publications] Kimura, Y., Seya et al.: "A short consensus repeat-containing complement regulatory protein of Lamprey, which participates in cleavage of lamprey C3"J.Immunol.. (in press). (2004)
[Publications] 上堀淳二, 赤澤隆, 松本美佐子, 瀬谷司: "BCG細胞壁骨格による樹状細胞の活性化とTLR臨床免疫"臨床免疫. 40(3). 248-253 (2003)
[Publications] 瀬谷司: "アジュバントを利用した樹状細胞の活性化と癌免疫療法への応用"現代医療別冊. 35(8). 139-145 (2003)
[Publications] 押海裕之, 松本美佐子, 瀬谷司: "Toll-like receptorと免疫療法"現代医療. 35(12). 149-154 (2003)
[Publications] 松本美佐子, 瀬谷司: "微生物成分を用いたヒト樹状細胞の制御:Toll-like receptorによるPAMP認識とシグナル伝達"Molecular Medicine. 40(5). 528-534 (2003)
[Publications] 松本美佐子, 押海裕之, 瀬谷司: "線維芽細胞のTLR3を介するインターレフェロン産生"臨床免疫. 44(3). 276-282 (2003)
[Publications] 松本美佐子, 押海裕之, 瀬谷司: "TLRを介したタイプイインターフェロン産生にかかわるアダプター分子TICAM-1"Molecular Medicine臨時増刊号免疫2004. 40. 194-200 (2003)
[Publications] 赤澤隆, 松本美佐子, 瀬谷司: "アジュバントを利用した樹状細胞の活性化と癌免疫療法への応用"現代医療. 35(8). 139-145 (2003)
[Publications] 瀬谷司, 上堀淳二, 赤澤隆: "BCG細胞壁骨格(CWS)による樹状細胞活性化の分子機構"Annual Review免疫. 216-223 (2004)

2003 Fiscal Year Annual Research Report

Innate immunityの活性化による抗がん免疫療法

Principal Investigator

瀬谷 司 大阪府立成人病センター研究所, 研究所長 (10301805)

Research Products

[Publications] Hazeki, K, Seya et al.: "TLR-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and-independent pathways."Eur.J.Immunol. 33. 740-747 (2003)

[Publications] Inoue, N, Seya et al.: "Disruption of the mouse CD46 caused an accelerated spontaneous acrosome reaction in sperm."Molec.Cell.Biol. 23. 2614-2622 (2003)

[Publications] Oshiumi, H., Seya et al.: "A novel adapter molecule that participates in Toll-like receptor-mediated interferon-beta induction"Nature Immunol. 4. 161-167 (2003)

[Publications] Oshiumi, H., Seya et al.: "Prediction of the prototype of the human Toll-like receptor gene family from the Pufferfish Fugu. rubripes genome"Immunogenetics. 54. 791-800 (2003)

[Publications] Takeuchi, J., Seya et al.: "TGF-betal Maintains the Skin Homeostasis by Modulating Responsiveness of Langerhans cells Against Bacteria"Biochem.Biophys.Res.Commun. 306. 674-679 (2003)

[Publications] Uehori, J, Seya et al.: "Simultaneous blocking of human Toll-like receptor 2 and 4 suppresses myeloid dendritic cell maturation induced by Mycobacterium bovis bacillus Calmette-Guerin (BCG)-peptidoglycan (PGN)."Infect. Immun. 71. 4238-4249 (2003)

[Publications] Shingai, M, Seya et al.: "Receptor usage by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis."J.Gen.Virol. 84. 2133-2143 (2003)

[Publications] Matsumoto, M, Seya et al.: "Subcellular localization of human Toll-like receptor 3 in human dendritic cells"J.Immunol. 171. 3154-3162 (2003)

[Publications] Oshiumi, H, Seya et al.: "Identification of the Toll-like receptor (TLR)-adapter that participates in TLR4-mediated interferon-beta induction."J.Biol.Chem. 278. 49751-79762 (2003)

[Publications] Akazawa T., Seya et al.: "Adjuvant-mediated tumor regression and tumor-specific CTL induction are impaired in MyD88-deficient mice"Cancer Res.. 64. 757-764 (2003)

[Publications] Tanabe, M, Seya et al.: "Up-regulation of a receptor for dsRNA, Toll-like receptor 3, in human myeloid dendritic cells via measles virus infection"Biochem.Biophys.Res.Commun. 311. 39-48 (2003)

[Publications] Honda, K, Seya et al.: "Selective contribution of IFN-a/b signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection"Proc.Natl.Acad.Sci.USA. 100. 10872-10877 (2003)

[Publications] Begum, N.A Seya et al.: "Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA subtraction in Human Macrophages"Infect.Immun. 72. 937-948 (2003)

[Publications] Matsumoto M., Seya et al.: "Minireview Toll-like receptor3 : A Link between Toll-like reeptor, Intereferon and Virus"Microbiol.Immunol.. 48(3). 147-154 (2004)

[Publications] Kimura, Y., Seya et al.: "A short consensus repeat-containing complement regulatory protein of Lamprey, which participates in cleavage of lamprey C3"J.Immunol.. (in press). (2004)

[Publications] 上堀淳二, 赤澤隆, 松本美佐子, 瀬谷司: "BCG細胞壁骨格による樹状細胞の活性化とTLR臨床免疫"臨床免疫. 40(3). 248-253 (2003)

[Publications] 瀬谷司: "アジュバントを利用した樹状細胞の活性化と癌免疫療法への応用"現代医療 別冊. 35(8). 139-145 (2003)

[Publications] 押海裕之, 松本美佐子, 瀬谷司: "Toll-like receptorと免疫療法"現代医療. 35(12). 149-154 (2003)

[Publications] 松本美佐子, 瀬谷司: "微生物成分を用いたヒト樹状細胞の制御:Toll-like receptorによるPAMP認識とシグナル伝達"Molecular Medicine. 40(5). 528-534 (2003)

[Publications] 松本美佐子, 押海裕之, 瀬谷司: "線維芽細胞のTLR3を介するインターレフェロン産生"臨床免疫. 44(3). 276-282 (2003)

[Publications] 松本美佐子, 押海裕之, 瀬谷司: "TLRを介したタイプイインターフェロン産生にかかわるアダプター分子TICAM-1"Molecular Medicine臨時増刊号 免疫2004. 40. 194-200 (2003)

[Publications] 赤澤隆, 松本美佐子, 瀬谷司: "アジュバントを利用した樹状細胞の活性化と癌免疫療法への応用"現代医療. 35(8). 139-145 (2003)

[Publications] 瀬谷司, 上堀淳二, 赤澤隆: "BCG細胞壁骨格(CWS)による樹状細胞活性化の分子機構"Annual Review免疫. 216-223 (2004)

瀬谷司大阪府立成人病センター研究所, 研究所長 (10301805)

[Publications] 瀬谷司: "アジュバントを利用した樹状細胞の活性化と癌免疫療法への応用"現代医療別冊. 35(8). 139-145 (2003)

[Publications] 松本美佐子, 押海裕之, 瀬谷司: "TLRを介したタイプイインターフェロン産生にかかわるアダプター分子TICAM-1"Molecular Medicine臨時増刊号免疫2004. 40. 194-200 (2003)