Targeting dendritic cell subsets with glycosylated antigens for cancer immunotherapy

• Project/Area Number: 23689009
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Juntendo University (2014-2015); St. Luke's College of Nursing (2013); The University of Tokyo (2011-2012)
• Principal Investigator: Denda-Nagai Kaori 順天堂大学, 医学部, 助教 (00313122)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,232,190 (Direct Cost: ¥12,486,300、Indirect Cost: ¥3,745,890); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥5,052,190 (Direct Cost: ¥3,886,300、Indirect Cost: ¥1,165,890); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 樹状細胞 / レクチン / 糖鎖 / がんワクチン / ターゲティング / 抗腫瘍ワクチン

Outline of Final Research Achievements

MUC1 antigens with glycans having a high affinity to mouse macrophage galactose-type C-type lectins expressed on a dermal dendritic subset were prepared for vaccination. Anti-MUC1 serum antibody response was significantly higher in mice immunized with glycosylated MUC1 as compared with MUC1 without glycosylation. The growth and metastasis of mouse colon carcinoma cells expressing MUC1 were suppressed by vaccination with the glycosylated MUC1. These results are suggested to be applicable in designing a novel cancer vaccine.

Research Products

• [Journal Article] 免疫系とバイオマテリアル：総論 (2015)
  • Author(s): 入村達郎、伝田香里
  • Journal Title: バイオマテリアル－生体材料－ Volume: 33(2) Pages: 8-15
• [Journal Article] The macrophage galactose-type lectin can function as an attachment and entry receptor for influenza virus. (2014)
  • Author(s): Ng WC, Liong S, Tate MD, Irimura T, Denda-Nagai K, Brooks AG, Londrigan SL, Reading PC.
  • Journal Title: Jornal of Virology Volume: 88(3) Issue: 3 Pages: 1659-72
  • DOI: 10.1128/jvi.02014-13
  • Peer Reviewed / Open Access
• [Journal Article] A unique dermal dendritic cell subset that skews the immune response toward Th2. (2013)
  • Author(s): 2.Murakami R, Denda-Nagai K, Hashimoto S, Nagai S, Hattori M, Irimura T.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e73270-e73270
  • DOI: 10.1371/journal.pone.0073270
  • Peer Reviewed / Open Access
• [Journal Article] Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo (2012)
  • Author(s): Sugiura D, Denda-Nagai K, Takashima M,他全7名
  • Journal Title: PLos One Volume: 7 (9) Issue: 9 Pages: e44770-e44770
  • DOI: 10.1371/journal.pone.0044770
  • Peer Reviewed
• [Journal Article] Mucin 21 in esophageal squamous epithelia and carcinomas: analysis with glycoform-specific monoclonal antibodies. (2012)
  • Author(s): Tian Y, Denda-Nagai K, Kamata-Sakurai M, Nakamori S, Tsukui T, Itoh Y, Okada K,Yi Y, Irimura T.
  • Journal Title: Glycobiology Volume: 22(9) Issue: 9 Pages: 1218-26
  • DOI: 10.1093/glycob/cws082
  • Peer Reviewed
• [Journal Article] Local effects of regulatory T cells in MUC1 transgenic mice potentiategrowth of MUC1 expressing tumor cells in vivo. (2012)
  • Author(s): Sugiura D, Denda-Naaai K, Takashima M, Murakami R, Nagai S, Takeda K, limura T.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Involvement of viral envelope GP2 1n Ebola virus entry into cellsexpressing the macrophage galactose-type C-type lectin. (2011)
  • Author(s): Usami K, Matsuno K, Igarashi M, Denda-Naaai K, Takada A, Irimura T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 407 Issue: 1 Pages: 74-78
  • DOI: 10.1016/j.bbrc.2011.02.110
  • Peer Reviewed
• [Presentation] MUC1 with truncated O-glycans induces humoral immune responses and suppresses the carcinoma growth and metastasis (2015)
  • Author(s): Kaori Denda-Nagai, Tatsuro Irimura
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [Presentation] MUC1 with truncated O-glycans induces humoral immune response to MUC1 and suppression of carcinoma growth and metastasis (2015)
  • Author(s): Miki Noji, Kaori Denda-Nagai, Airi Namba2 and Tatsuro Irimura
  • Organizer: LMU-UTokyo Symposium
  • Place of Presentation: The Innovation and Founding Center Biotechnology (IZB), Munich, Germany
  • Year and Date: 2015-10-29
  • Int'l Joint Research
• [Presentation] マクロファージガラクトース型C型レクチン(MGL/CD301)によって制御される免疫応答 (2015)
  • Author(s): 伝田香里
  • Organizer: 第34回日本糖質学会年会
  • Place of Presentation: 東京大学
  • Year and Date: 2015-07-31
  • Invited
• [Presentation] MUC1 with truncated O-glycans induces humoral immune response to MUC1 and suppression of carcinoma growth and metastasis (2015)
  • Author(s): Kaori Denda-Nagai, Airi Namba, Miki Noji, Tatsuro Irimura
  • Organizer: 13th International Workshop on Mucins in Health and diseases
  • Place of Presentation: Robinson College, Cambridge, UK
  • Year and Date: 2015-07-18
  • Int'l Joint Research
• [Presentation] 糖鎖付加MUC1に対する免疫応答による癌の増殖と転移の抑制 (2015)
  • Author(s): 難波愛理、伝田香里、野地美樹、入村達郎
  • Organizer: 第135年会日本薬学会
  • Place of Presentation: 兵庫医療大学
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] マクロファージガラクトース型C型レクチン（MGL/CD301）による炎症と免疫の制御 (2014)
  • Author(s): 伝田香里、入村達郎
  • Organizer: 第12回糖質科学コンソーシアムシンポジウム
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2014-12-04 – 2014-12-05
  • Invited
• [Presentation] MGL1/CD301陽性細胞の免疫と炎症の制御における重要性 (2014)
  • Author(s): 伝田香里、入村達郎
  • Organizer: 糖鎖免疫Glyco-Immunology 2014
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2014-02-17 – 2014-02-18
  • Invited
• [Presentation] Differential glycosylation of MUC1 has an impact on cancer immunity through the function of MGL1/MGL2 (2013)
  • Author(s): 木村翔彦、伝田香里、入村達郎
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-03 – 2013-10-05
• [Presentation] ムチン２１による糖鎖構造依存的アポトーシス抑制機構の解明 (2013)
  • Author(s): 田園、伝田香里、小川利久、入村達郎
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-09-11 – 2013-09-13
• [Presentation] エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明 (2012)
  • Author(s): 藤平陽彦、宇佐美克明、伝田香里、松野啓太、篠原康郎、佐藤あやの、高田礼人、掛樋一晃、入村達郎
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2012-12-15
• [Presentation] エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明 (2012)
  • Author(s): 藤平陽彦、宇佐美克明、伝田香里、松野啓太、篠原康郎、佐藤あやの、 高田礼人、掛樋一晃、入村達郎
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、福岡県
  • Year and Date: 2012-12-15
• [Presentation] MGL1-dependent IL-10 induction in colonic macrophages by commensal bacteria is mediated by the Syk-CARD9 pathway (2012)
  • Author(s): Denda-Nagai K, Kurashina R, Hara H, Yoshida H, Irimura T
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2012-12-07
• [Presentation] MGL1-dependent IL-10 induction in colonic macrophages by commensalbacteria is mediated by the Syk-CARD9 pathway (2012)
  • Author(s): Denda-Naaai K, Kurashina R,Hara H, Yoshida H, Irimura T
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場、兵庫県
  • Year and Date: 2012-12-07
• [Presentation] Dermal dendritic cells expressing MGL2 skew the immune response toward Th2 in contact hypersensitivity (2012)
  • Author(s): Denda-Nagai K, Murakami R, Hashimoto S, Nagai S, Irimura T
  • Organizer: 12^<th> International symposium on dendritic cells
  • Place of Presentation: EXCO, Daegu, Korea
  • Year and Date: 2012-10-11
• [Presentation] Dermal dendritic cells expressing MGL2 skew the immune response towardTh2 1n contact hypersensitivity (2012)
  • Author(s): Denda-Naaai K, Murakami R,Hashimoto S, Nagai S, Irimura T
  • Organizer: 12th International symposium on dendritic cells
  • Place of Presentation: EXCO, Daegu, Korea
  • Year and Date: 2012-10-11
• [Presentation] IL-10 induction in colonic macrophages by commensal bacteria is dependent on MGL1 and mediated by the Syk-CARD9 pathway (2012)
  • Author(s): Denda-Nagai K, Kurashina R, Hara H, Yoshida H, Irimura T.
  • Organizer: 20^<th> International symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: Sanjyo Conference Hall, The University of Tokyo, Japan
  • Year and Date: 2012-06-16
• [Presentation] IL-10 induction in colonic macrophages by commensal bacteria isdependent on MGL1 and mediated by the Syk-CARD9 pathway (2012)
  • Author(s): Denda-Naaai K, Kurashina R,Hara H, Yoshida H, Irimura T.
  • Organizer: 20th International symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: Sanjyo Conference Hall,The University of Tokyo
  • Year and Date: 2012-06-16
• [Presentation] Dermal dendritic cell expressing macrophage galactose-type C-type lectin 2(MGL2/CD3O1b) skew the immune response toward Th2 1n vivo in contacthypersensitivity (2011)
  • Author(s): Murakami R, Denda-Naaai K,Irimura T
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ、千葉県
  • Year and Date: 2011-11-29
• [Presentation] The mechanism involved in the induction of IL-10 1n intestinal macrophages through the recognition of commensal bacteria by a C-type lectin, MGL1/CD3O1a (2011)
  • Author(s): Kurashina R, Denda-Naaai K,Hara H, Yoshida H, Irimura T
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ、千葉県
  • Year and Date: 2011-11-28
• [Presentation] MUC1DNAと樹状細胞の併用ワクチンによる実験的炎症性大腸発癌の抑制 (2011)
  • Author(s): 伝田香里、木村翔彦、入村達郎
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場、愛知県
  • Year and Date: 2011-10-05
• [Presentation] Structural characteristic of Ebola viral GP1 involved in attachment andinfection (2011)
  • Author(s): 藤平陽彦、宇佐美克明、伝田香里、山田佳太、松野啓太、篠原康郎、高田礼人、掛樋一晃、入村達郎
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館、京都府
  • Year and Date: 2011-09-23
• [Presentation] Dermal dendritic cells expressing macrophage galactose-type C-type lectin2 (MGL2/CD3O1b) are likely to render the Th2-type immune response (2011)
  • Author(s): Murakami R, Denda-Naaai K,Irimura T
  • Organizer: JSICR-MCB2011
  • Place of Presentation: ANA Gate Tower HotelOsaka
  • Year and Date: 2011-05-25
• [Book] MGL/CD301 as a Unique C-Type Lectin Expressed on Dendritic Cells and Macrophages. In: C-Type Lectin Receptors in Immunity (Sho Yamasaki eds.) (2016)
  • Author(s): Kaori Denda-Nagai, Tatsuro Irimura
  • Publisher: Springer