Anti-tumor vaccine by the use of antigen targeting to lectins expressed on dendritic cells

• Project/Area Number: 21790144
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: DENDA Kaori The University of Tokyo, 大学院・薬学系研究科, 助教 (00313122)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 樹状細胞 / レクチン / ターゲティング / 抗腫瘍ワクチン / 糖鎖

Research Abstract

The subcutaneous injection of anti-MGL2 monoclonal antibodies successfully targeted antigens to the cells expressing MGL2 in mice. The antigens taken up through MGL2 were presented to antigen-specific CD4^+ T cells and led to an efficient antibody response. Since mouse MGL2 is thought to be a human MGL ortholog, these results are suggested to be able to apply to the development of novel vaccine.

Research Products

• [Journal Article] Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin. (2011)
  • Author(s): Usami K, Matsuno K, Igarashi M, Denda-Nagai K, Takada A, Irimura T.
  • Journal Title: Biochem Biophys Res Commun. 407 Pages: 74-78
• [Journal Article] Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin. (2011)
  • Author(s): Usami K, Matsuno K, Igarashi M, Denda-Nagai K, Takada A, Irimura T.
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Pages: 74-78
  • Peer Reviewed
• [Journal Article] The organ microenvironment plays significant roles through Fas ligand in vaccine-induced CD4^+ T cell dependent suppression of tumor growth at the orthotopic site. (2010)
  • Author(s): Sugiura D, Denda-Nagai K, Takeda K, Irimura T.
  • Journal Title: Cancer Sci. 101 Pages: 1965-1969
• [Journal Article] Mucin 21/epiglycanin modulates cell adhesion. (2010)
  • Author(s): Yi Y, Kamata-Sakurai M, Denda-Nagai K, Itoh T, Okada K, Ishii-Schrade K, Iguchi A, Sugiura D, Irimura T.
  • Journal Title: J Biol Chem. 285 Pages: 21233-21240
• [Journal Article] Distribution and function of macrophage galactose-type C-type lectin 2 (MGL2/CD301b) : Efficient uptake and presentation of glycosylated antigens by dendritic cells. (2010)
  • Author(s): Denda-Nagai K, Aida S, Saba K, Suzuki K, Moriyama S, Oo-Puthinan S, Tsuiji M, Morikawa A, Kumamoto Y, Sugiura D, Kudo A, Akimoto Y, Kawakami H, Bovin NV, Irimura T.
  • Journal Title: J Biol Chem. 285 Pages: 19193-19204
• [Journal Article] Distribution and function of macrophage galactose-type C-type lectin 2 (MGL2/CD301b) : Efficient uptake and presentation of glycosylated antigens by dendritic cells. (2010)
  • Author(s): Denda-Nagai K, Aida S, Saba K, Suzuki K, Moriyama S, Oo-Puthinan S, Tsuiji M, Morikawa A, Kumamoto Y, Sugiura D, Kudo A, Akimoto Y, Kawakami H, Bovin NV, Irimura T.
  • Journal Title: J Biol Chem Volume: 285 Pages: 19193-19204
  • Peer Reviewed
• [Journal Article] Mucin 21/epiglycanin modulates cell adhesion. (2010)
  • Author(s): Yi Y, Kamata-Sakurai M, Denda-Nagai K, Itoh T, Okada K, Ishii-Schrade K, Iguchi A, Sugiura D, Irimura T.
  • Journal Title: J Biol Chem Volume: 285 Pages: 21233-21240
  • Peer Reviewed
• [Journal Article] The organ microenvironment plays significant roles through Fas ligand in vaccine-induced CD4^+ T cell dependent suppression of tumor growth at the orthotopic site. (2010)
  • Author(s): Sugiura D, Denda-Nagai K, Takeda K, Irimura T.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1965-1969
  • Peer Reviewed
• [Journal Article] Distribution and function of macrophage galactose-type C-type lectin 2(MGL2/CD301b): Efficient uptake and presentation of glycosylated antigens by dendritic cells (2010)
  • Author(s): Denda-Nagai K, Aida, S, Saba K, Suzuki K, Moriyama S, Oo-Puthinan S, Tsuiji M, Morikawa A, Kumamoto Y, Sugiura D, Kudo A, Akimoto Y, Kawakami H, Bovin NV, Irimura T.
  • Journal Title: J Biol Chem (in press)
  • Peer Reviewed
• [Journal Article] MGL2 dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo. (2009)
  • Author(s): Kumamoto Y, Denda-Nagai K, Aida S, Higashi N, Irimura T.
  • Journal Title: PLoS ONE. 4
• [Journal Article] MGL2 dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo (2009)
  • Author(s): Kumamoto Y, Denda-Nagai K, Aida S, Higashi N, Irimura T.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Presentation] Dermal dendritic cells expressing macrophage galactose-type C-type lectin 2 (MGL2/CD301b) are likely to render the Th2-type immune response. (2011)
  • Author(s): Murakami R, Denda-Nagai K, Irimura T.
  • Organizer: JSICR-MCB2011
  • Place of Presentation: ANA Gate Tower Hotel Osaka, Osaka
  • Year and Date: 2011-05-25
• [Presentation] Strain-Dependent Glycosylation of Ebola Viral Envelope Glycoproteins Determines their Infectivity. (2010)
  • Author(s): Usami K, Fujihira H, Denda-Nagai K, Yamada K, Matsuno K, Takada A, Kakehi K, Irimura T.
  • Organizer: 2010 Annual Conference of the Society for Glycobiology
  • Place of Presentation: TradeWinds Island Grand Resort St Pete Beach, FL, USA
  • Year and Date: 2010-11-10
• [Presentation] Roles of Macrophage Galactose-Type C-Type Lectin 2 in Efficient Uptake and Presentation of Antigens Having GalNAc Residues by Dendritic Cells. (2010)
  • Author(s): Denda-Nagai K, Irimura T.
  • Organizer: 2010 Annual Conference of the Society for Glycobiology
  • Place of Presentation: TradeWinds Island Grand Resort St Pete Beach, FL, USA
  • Year and Date: 2010-11-10
• [Presentation] Distribution and function of macrophage galactose-type C-type lectin 2(MGL2/CD301b) (2010)
  • Author(s): Denda-Nagai K, Murakami R, Irimura T.
  • Organizer: 11^<th> International Symposium on Dendritic Cells in Fundamental and Clinical Immunology.
  • Place of Presentation: Palazzo dei Congressi, Lugano, Switzerland
  • Year and Date: 2010-09-28
• [Presentation] Distribution and function of macrophage galactose-type C-type lectin 2 (MGL2/CD301b) (2010)
  • Author(s): Denda-Nagai K, Murakami R, Irimu
  • Organizer: 11^<th> International Symposiumon Dendritic Cells in Fun damental and Clinical Immunology
  • Place of Presentation: Palazzo dei Congressi, Lugano, Switzerland
  • Year and Date: 2010-09-28
• [Presentation] Detection of MUC21 in sera and ascitic fluid from mice bearing human tumors (2010)
  • Author(s): Tian Y, Kamata-Sakurai M, Denda-Nagai K, Irimura T.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2010-09-24
• [Presentation] Mucin21/epiglycanin in malignant behavior of cancer cells (2010)
  • Author(s): Irimura T, Denda-Nagai K, Tian Y.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2010-09-24
• [Presentation] Mucin21/epiglycanin in malignant behavior of cancer cells. (2010)
  • Author(s): Irimura T, Denda-Nagai K, Tian Y.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] Detection of MUC21 in sera and ascitic fluid from mice bearing human tumors. (2010)
  • Author(s): Tian Y, Kamata-Sakurai M, Denda-Nagai K, Irimura T.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] A carcinoma-associated mucin, Muc21/epiglycanin,modulates cell adhesion and survival (2010)
  • Author(s): Zhao J, Yi Y, Denda-Nagai K, Hayakawa Y, Kamata-Sakurai M, Akimoto Y, Kawakami H, Irimura T.
  • Organizer: 第30回日本分子腫瘍マーカー研究会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2010-09-21
• [Presentation] A carcinoma-associated mucin, Muc21/epiglycanin, modulates cell adhesion and survival. (2010)
  • Author(s): Zhao J, Yi Y, Denda-Nagai K, Hayakawa Y, Kamata-Sakurai M, Akimoto Y, Kawakami H, Irimura T.
  • Organizer: 第30回日本分子腫瘍マーカー研究会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-21
• [Presentation] Roles of macrophage galactose-type C-type lectin 2 (MGL2/CD301b) in the immune response. (2010)
  • Author(s): Denda-Nagai K, Irimura T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe Portpia Hotel & Kobe International Exhibition Hall, Kobe
  • Year and Date: 2010-08-24
• [Presentation] Roles of macrophage galactose-type C-type lectin 2(MGL2/CD301b)in the immune response. (2010)
  • Author(s): Denda-Nagai K, Irimura T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe Portpia Hotel & Kobe International Exhibition Hall
  • Year and Date: 2010-08-24
• [Presentation] Muc21/epiglycanin Modulates Cancer Cell Survival (2010)
  • Author(s): Zhao J, Kamata-Sakurai M, Yi Y, Denda-Nagai K, Irimura T.
  • Organizer: GlycoT 2010/7^<th> International Symposium on Glycosyltransferases
  • Place of Presentation: KFC-Kokusai Fashion Center, Tokyo
  • Year and Date: 2010-07-31
• [Presentation] Muc21/epiglycanin Modulates Cancer Cell Survival. (2010)
  • Author(s): Zhao J, Kamata-Sakurai M, Yi Y, Denda-Nagai K, Irimura T.
  • Organizer: 7^<th> International Symposium on Glycosyltransferases
  • Place of Presentation: KFC-Kokusai Fashion Center, Tokyo
  • Year and Date: 2010-07-31
• [Presentation] Detection of MUC21/Human-Epiglycanin by Monoclonal Antibody (2010)
  • Author(s): Tian Y, Kamata-Sakurai M, Denda-Nagai K, Ogawa T, Irimura T.
  • Organizer: 第28回内藤コンファレンス
  • Place of Presentation: 湘南国際村センター、神奈川
  • Year and Date: 2010-07-29
• [Presentation] Detection of MUC21/Human-Epiglycanin by Monoclonal Antibody. (2010)
  • Author(s): Tian Y, Kamata-Sakurai M, Denda-Nagai K, Ogawa T, Irimura T.
  • Organizer: 第28回内藤コンファレンス
  • Place of Presentation: 湘南国際村センター
  • Year and Date: 2010-07-29
• [Presentation] 接触過敏症におけるMGL1およびMGL2の位置づけ (2010)
  • Author(s): 村上龍一、隈本洋介、伝田香里、入村達郎
  • Organizer: 第11回Pharmaco-Hemotology Symposium
  • Place of Presentation: 日本薬学会長井記念ホール、東京
  • Year and Date: 2010-06-18
• [Presentation] 接触過敏症におけるMGL1およびMGL2の位置づけ (2010)
  • Author(s): 村上龍一、隈本洋介、伝田香里、入村達郎
  • Organizer: 第11回Pharmaco-Hemotology Symposium
  • Place of Presentation: 日本薬学会長井記念ホール
  • Year and Date: 2010-06-18
• [Presentation] Distribution and immunological implications of MGL2. (2010)
  • Author(s): Denda-Nagai K.
  • Organizer: 18^<th> International Symposium on Molecular Cell Biology of Macrophages 2010
  • Place of Presentation: Kumamoto Parea Hall, Kumamoto
  • Year and Date: 2010-05-20
• [Presentation] Distribution and immunological implications of MGL2 (2010)
  • Author(s): Denda-Nagai K
  • Organizer: 18^<th> International Symposium on Molecular Cell Biology of Macrophages 2010
  • Place of Presentation: Kumamoto Parea Hall
  • Year and Date: 2010-05-20
• [Presentation] ヒトMUC21細胞外ドメインに対するモノクローナル抗体の樹立 (2010)
  • Author(s): 田園、櫻井実香、伝田香里、入村達郎
  • Organizer: 第130年会日本薬学会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2010-03-28
• [Presentation] Effect of MUC1 plasmid DNA and BM-DCs vaccination in an experimental colon carcinogenesis in MUC1 transgenic mice. (2010)
  • Author(s): Murwanti R, Sugiura D, Denda-Nagai K, Kamata-Sakurai M, Irimura T.
  • Organizer: 8th Joint Conference of the AACR and JCA "Cancer Genomics, Epigenomics, and The Development of Novel Therapeutics."
  • Place of Presentation: Hilton Waikoloa Village, Hawaii, USA
  • Year and Date: 2010-02-06
• [Presentation] A Streptococcus cell surface component potentially involves with the suppression of inflammatory bowel disease through its recognition by MGL1/CD301a and induction of IL-10 (2009)
  • Author(s): Kurashina R, Denda-Nagai K, Irimura T.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-04
• [Presentation] Antigen-specific regulatory T cells in MUC1 transgenic mice (2009)
  • Author(s): Sugiura D, Denda-Nagai K, Takeda K, Yagita H, Irimura T.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-03
• [Presentation] 接触過敏症におけるMGL2を発現する真皮樹状細胞の重要性/MGL2+ dermal dendritic cells in contact hypersensitivity (2009)
  • Author(s): Denda-Nagai K, Kumamoto Y, Higashi N, Irimura T.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] MGL2+ dermal dendritic cells in contact hypersensitivity (2009)
  • Author(s): Denda-Nagai K, Kumamoto Y, Higashi N, Irimura T.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Roles of MGL/CD301 in inflammatory bowel diseases : recognition of glycoconjugates on commensal bacteria. (2009)
  • Author(s): Kurashina R, Denda-Nagai K, Saba K, Irimura T.
  • Organizer: 20^<th> European Joint Glycobiology Meeting 2009
  • Place of Presentation: Koln, Germaney
  • Year and Date: 2009-11-10
• [Presentation] Roles of MGL/CD301 in inflammatory bowel diseases : recognition of glycoconjugates on commensal bacteria (2009)
  • Author(s): Kurashina R, Denda-Nagai K, Saba K, Irimura T.
  • Organizer: 20^<th> European Joint Glycobiology Meeting 2009
  • Place of Presentation: Koln, Germaney
  • Year and Date: 2009-11-10
• [Presentation] MGL/CD301を介するエボラウイルス感染増強に関わる表層糖蛋白質の構造的特徴 (2009)
  • Author(s): 宇佐美克明、松野啓太、五十嵐学、伝田香里、高田礼人、入村達郎
  • Organizer: 第82回日本生化学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-24
• [Presentation] A C-TYPE LECTIN MGL1/CD301A PLAYS AN ANTI-INFLAMMATORY ROLE THROUGH THE RECOGNITION OF COMMENSAL BACTERIA IN MURINE EXPERIMENTAL COLITIS. (2009)
  • Author(s): Denda-Nagai K, Saba K, Irimura T.
  • Organizer: The 9th World Congress on Inflammation
  • Place of Presentation: Keio Plaza Hotel Tokyo
  • Year and Date: 2009-07-08
• [Presentation] A C-TYPE LECTIN MGL1/CD301A PLAYS AN ANTI-INFLAMMATORY ROLE THROUGH THE RECOGNITION OF COMMENSAL BACTERIA IN MURINE EXPERIMENTAL COLITIS (2009)
  • Author(s): Denda-Nagai K, Saba K, Irimura T.
  • Organizer: The 9th World Congress on Inflammation
  • Place of Presentation: Keio Plaza Hotel Tokyo
  • Year and Date: 2009-07-08
• [Presentation] MGL2+ dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo. (2009)
  • Author(s): Denda-Nagai K, Kumamoto Y, Aida S, Higashi N, Irimura T.
  • Organizer: 17^<th> International Symposium on Molecular Cell Biology of MACROPHAGES 2009
  • Place of Presentation: KKR Hotel Kanazawa
  • Year and Date: 2009-07-03
• [Presentation] MGL2^+ dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo (2009)
  • Author(s): Denda-Nagai K, Kumamoto Y, Aida S, Higashi N, Irimura T.
  • Organizer: 17^<th> International Symposium on Molecular Cell Biology of MACROPHAGES 2009
  • Place of Presentation: KKR Hotel Kanazawa
  • Year and Date: 2009-07-03
• [Presentation] Epiglycanin/MUC21 as a potential marker for thyroid carcinomas. (2009)
  • Author(s): Okada K, Kamata-Sakurai M, Itoh Y, Denda-Nagai K, Ogawa T, Irimura T.
  • Organizer: 2009 AACR Annual Meeting
  • Place of Presentation: Colorado Convention Center, Denver, CO, USA
  • Year and Date: 2009-04-21
• [Presentation] Unique effector mechanisms induced by vaccination with MUC1 DNA in the rejection of colon arcinoma growth at orthotopic sites and metastases. (2009)
  • Author(s): Sugiura D, Aida S, Denda-Nagai K, Kamata-Sakurai M, Takeda K, Yagita H, Irimura T.
  • Organizer: 2009 AACR Annual Meeting
  • Place of Presentation: Colorado Convention Center, Denver, CO, USA
  • Year and Date: 2009-04-19
• [Presentation] Unique effector mechanisms induced by vaccination with MUC1 DNA in the rejection of colon carcinoma growth at orthotopic sites and metastases (2009)
  • Author(s): Sugiura D, Aida S, Denda-Nagai K, Kamata-Sakurai M, Takeda K, Yagita H, Irimura T.
  • Organizer: AACR 100^<th> Annual Meeting 2009
  • Place of Presentation: Colorado convention Center, Denver Co.
  • Year and Date: 2009-04-19
• [Presentation] Epiglycanin/MUC21 as a potential marker for thyroid carcinomas (2009)
  • Author(s): Okada K, Kamata-Sakurai M, Itoh Y, Denda-Nagai K, Ogawa T, Irimura T.
  • Organizer: AACR 100^<th> Annual Meeting 2009
  • Place of Presentation: Colorado convention Center, Denver Co.
  • Year and Date: 2009-04-19
• [Book] Seriesモデル動物利用マニュアル 生物機能モデルと新しいリソース・リサーチツール(小幡裕一、城石俊彦、芦川忠夫、田中啓二、米川博通編)(マクロファージガラクトース型C型レクチン1(MGL1)および(MGL2)) (2011)
  • Author(s): 伝田香里、入村達郎
  • Publisher: 株式会社エル・アイ・シー
• [Book] Seriesモデル動物利用マニュアル 生物機能モデルと新しいリソース・リサーチツール(小幡裕一、城石俊彦、芦川忠夫、田中啓二、米川博通編)(「マクロファージガラクトース型C型レクチン1(MGL1)および(MGL2)」) (2011)
  • Author(s): 伝田香里、入村達郎
  • Publisher: 株式会社エル・アイ・シー
• [Book] 創薬科学の魅力-東京大学大学院薬学系研究科からの発信-(杉山雄一、柴崎正勝、長野哲雄、松木則夫編)(糖鎖生命科学を通して免疫と病態を捉え直す) (2010)
  • Author(s): 入村達郎、東伸昭、伝田香里、櫻井実香
  • Publisher: 廣川書店
• [Book] 「糖鎖生命科学を通して免疫と病態を捉え直す」、『創薬科学の魅力-東京大学大学院薬学系研究科からの発信-(杉山雄一、柴崎正勝、長野哲雄、松木則夫編)』 (2010)
  • Author(s): 入村達郎、東伸昭、伝田香里、櫻井実香
  • Publisher: 廣川書店