Suppression mechanism for anti-tumor immune response through sialyl In antigen

• Project/Area Number: 19590420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: IKEHARA Yuzuru National Institute of Advanced Industrial Science and Technology, 糖鎖医工学研究センター, 研究チーム長 (10311440)
• Co-Investigator(Kenkyū-buntansha): TSUJIMURA Kunio 浜松医科大学, 感染症学講座, 准教授 (10227407)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: シアル酸 / がん / 腹腔内転移 / 腫瘍免疫 / シアリルTn / ELISPOTアッセイ / TH1 / 2細胞 / がん関連糖鎖 / 病理学 / 糖鎖 / 癌

Research Abstract

STn 抗原を発現するヒト胃がんは、腹腔内に播種性に進展しやすく、有為に予後不良となる事が知られている。本研究では、STn 抗原を産生する様に改変した細胞を用い、OVA をモデルがん抗原として検討した。STn 抗原を産生する様に改変した細胞を接種したマウスのリンパ組織では、不活性型ST6GalNAc I 遺伝子を導入したSTn 抗原発現の無い細胞を接種したマウスに比べて、免疫抑制をする細胞がより多く誘導され、OVA 抗原に特異的な細胞障害性T 細胞数も抑制される事を見いだした。また、シアル酸被覆リポソームにOVA を封入して投与するモデル実験でも、同様の結果を得る事ができた。これらの事は、STn 抗原等シアル酸を有為に高発現する細胞は、腫瘍免疫による排除を効率良く回避できるメカニズムの存在を示唆する。

Research Products

• [Journal Article] Immunization of oligomannose-coated liposome-entrapped NcGRA7 protects dams and offspring from Neospora caninum infection in mice (2009)
  • Author(s): Nishikawa Y, Zhang H, Ikehara Y, Kojima N, Xuan X, Yokoyama N
  • Journal Title: Clin Vaccine Immunol [Epub ahead of print]
• [Journal Article] Igarashi I. Isolation and pathogenic characterization of an OB1 variant of Babesiarodhaini which has a glycophorin A independent invasion pathway to murine red blood cells (2009)
  • Author(s): Takabatake N., Iseki H., Ikehara Y., Kanuka H., Yokoyama N., Sekimizu K
  • Journal Title: Veterinary Parasitology 5;159(2) Pages: 97-104
• [Journal Article] Strategy for Glycoproteomics: Identification of Glyco-Alteration Using Multiple Glycan Profiling Tool (2009)
  • Author(s): Ito H, Kuno A, Sawaki H, Sogabe M, Ozaki H, Tanaka Y, Mizokami M, Shoda JI, Angata T, Sato T, Hirabayashi J, Ikehara Y, Narimatsu H.
  • Journal Title: J Proteome Res [Epub ahead of print]
• [Journal Article] Isolation and pathogenic characterization of an OB1 variant of Babesia rodhaini which has a glycophorin A independent invasion pathway to murine red blood cells (2009)
  • Author(s): Takabatake N.
  • Journal Title: Veterinary Parasitology 159(2) Pages: 97-104
  • Peer Reviewed
• [Journal Article] Strategy for Glycoproteomics : Identification of Glyco-Alteration Using Multiple Glycan Profiling Tool (2009)
  • Author(s): Ito H
  • Journal Title: J Proteome Res. (In press)
  • Peer Reviewed
• [Journal Article] Immunization of oligomannose-coated liposome-entrapped NcGRA7 protects dams and offspring from Neospora caninum infection in mice (2009)
  • Author(s): Nishikawa Y
  • Journal Title: Clin Vaccine Immunol. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Tsujimura K. and Kojima N.: Effective induction of anti-tumor immune responses with Oligomannose-Coated Liposome targeting to intraperitoneal phagocytic cells (2008)
  • Author(s): Ikehara Y.*, Shiuchi N., Kabata-Ikehara S., Nakanishi H., Yokoyama N., Takagi H., Nagata T., Koide Y., Kuzushima K., Takahashi T
  • Journal Title: Cancer Letters 260(1-2) Pages: 137-145
• [Journal Article] Effect of CD4+CD25+ T cell-depletion on acute lethal infection of mice with Trypanosoma congolense (2008)
  • Author(s): Namangala B, Yokoyama N, Ikehara Y,Taguchi O, Tsujimura K, Sugimoto C,Inoue N
  • Journal Title: Journal of Veterinary Medical Science 70(8)
  • NAID: 110006878921
• [Journal Article] Oligomannose-coated liposomes as a therapeutic antigen-delivery and an adjuvant vehicle for induction of in vivo tumor immunity (2008)
  • Author(s): Kojima N, Biao L, Nakayama T, Ishii M, Ikehara Y, Tsujimura K
  • Journal Title: J Control Release 2;129(1) Pages: 26-32
• [Journal Article] Immunocytochemical for intracellar dynamics of C1GalT associatedwith moleculer chaperone (2008)
  • Author(s): Narimatsu Y., Ikehara Y., Iwasaki H., Nonomura C., Sato T., Nakanishi H., and Narimatsu H
  • Journal Title: Biochem. Biophys. Res. Commun 366(1) Pages: 199-205
• [Journal Article] Effective induction of anti-tumor immune responses with Oligomannose-Coated Liposome targeting to intraperitoneal phagocytic cells (2008)
  • Author(s): Ikehara Y.
  • Journal Title: Cancer Letters 260(1-2) Pages: 137-145
  • Peer Reviewed
• [Journal Article] Immunocytochemical for intracellar dynamics of C1GalT associated with moleculerchaperone, Cosmc (2008)
  • Author(s): Narimatsu Y.
  • Journal Title: Biochem. Biophys. Res. Commun. 366(1) Pages: 199-205
  • Peer Reviewed
• [Journal Article] Effect of CD4+CD25+T cell-depletion on acute lethal infection of mice with Trypanosoma congolense (2008)
  • Author(s): Namangala B
  • Journal Title: Journal of Veterinary Medical Science 70(8) Pages: 751-759
  • Peer Reviewed
• [Journal Article] Oligomannose-coated liposomes as a therapeutic antigen-delivery and an adjuvant vehicle for induction of in vivo tumor immunity (2008)
  • Author(s): Kojima N
  • Journal Title: J Control Release 129(1) Pages: 26-32
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): 済木育夫(編さん)
  • Journal Title: がん転移研究の実験手法 金芳堂 Pages: 318-323
• [Journal Article] (2008)
  • Author(s): 池原譲
  • Journal Title: 臨床糖鎖バイオマーカーの開発-糖鎖機能の解明とその応用(メディカルドウ) 11号
• [Journal Article] Babesia bovis: Subcellular localization of host erythrocyte membrane components during their asexual growth (2007)
  • Author(s): Okamura M., Yokoyama N., Takabatake N., Okubo K., Ikehara Y., Igarashi I
  • Journal Title: Experimental Parasitology 116(1)
  • NAID: 120006390254
• [Journal Article] Mice lacking a1,3-fucosyltransferase IX demonstrate disappearance of Lewis x structure in brain and increased anxiety-like behaviors (2007)
  • Author(s): Kudo T., Fujii T., Ikegami S., Inokuchi K., Takayama Y., Ikehara Y., Nishihara S., Togayachi A,. Takahashi S., Tachibana K., Yuasa S, Narimatsu H
  • Journal Title: Glycobiology 17(1) Pages: 1-9
• [Journal Article] Modification of host erythrocyte membranes by trypsin and chymotrypsin treatmentsand effects on the in vitro growth of bovine and equine babesia parasites (2007)
  • Author(s): Okamura M., Yokoyama N., Takabatake N., Okubo K., Ikehara Y., Igarashi I
  • Journal Title: Journal of Parasitology 93(1) Pages: 208-211
• [Journal Article] Involvement of A Host Erythrocyte Sialic Acid Content In Babesia Bovis Infection (2007)
  • Author(s): Takabatake N., Okamura M., Yokoyama N., Okubo K., Ikehara Y., Igarashi I
  • Journal Title: The Journal of Veterinary Medical Science 69(10) Pages: 999-1004
  • NAID: 110006418717
• [Journal Article] Polylactosamine on glycoproteins influences basal levels of lymphocyte and macrophage activation (2007)
  • Author(s): Togayachi A., Kozono Y, Ishida H., Abe S., Suzuki N., Tsunoda Y., Hagiwara K., Kuno A., Ohkura T., Sato N., Sato T., Hirabayashi J., Ikehara Y., Tachibana K., and Narimatsu H
  • Journal Title: Proc Natl Acad Sci U S A. 104(40) Pages: 15829-34
• [Journal Article] Glycophorin A knockout mice, which lost sialoglycoproteins from the red blood cell membrane, are resistant to lethal infection of Babesia rodhaini (2007)
  • Author(s): Takabatake N., Okamura M., Yokoyama N., Ikehara Y., Akimitsu N., Arimitsu N, Hamamoto H., Sekimizu K., Suzuki H., and Igarashi I
  • Journal Title: Veterinary Parasitology 148(2) Pages: 93-101
• [Journal Article] Solitarybone metastasis as the first clinical manifestation in a patient with small bowel adenocarcinoma (2007)
  • Author(s): Yamada K, Ikehara Y., Nakanishi H, Kozawa E, Tatematsu M, Sugiura H
  • Journal Title: J Orthop Sci Nov;12(6)
• [Journal Article] Babesia bovis:Subcellular localization of host erythrocyte membrane components during their asexual growth (2007)
  • Author(s): Okamura M., Yokoyama N., Takabatake N., Okubo K., IkeharaY., Igarashi I.
  • Journal Title: Experimental Parasitology 116 Pages: 91-94
  • Peer Reviewed
• [Journal Article] Mice lacking al, 3-fUcosyltransferase IX demonstrate disappearance of Lewis xstructure in brain and increased anxiety-like behaviors (2007)
  • Author(s): Kudor T., Fujii T., Ikegami S., Inokuchi K., Takayama Y., Ikehara Y., et. al.
  • Journal Title: Glycobiology 17 Pages: 1-9
  • Peer Reviewed
• [Journal Article] Modification of host erythrocyte membranes by trypsin and chymotrypsin treatments and effects on the in vitro growth of bovine and equine babesia parasltes (2007)
  • Author(s): Okamura M., YOkoyama N., Takabatake N., Okubo K., Ikehara Y., Igarashi I.
  • Journal Title: Journal of Parasitology 93 Pages: 208-211
  • Peer Reviewed
• [Journal Article] Involvement of A Host Erythrecyte Sialic Acid Content In Babesia Bovis Infection (2007)
  • Author(s): Takabatake N., Okamura M., Yokoyama N., Okubo K., Ikehara Y., Igarashi I.
  • Journal Title: The Journal of Veterinary Medical Science 69 Pages: 999-1004
  • Peer Reviewed
• [Journal Article] Polylactosamine on glycoproteins influences basal levels of lymphocyte and macrophage activation (2007)
  • Author(s): Togayachi A., Kozono Y, Ishida H., Abe S., Suzuki N., Tsunoda Y., Hagiwara K., Kuno A., Ohkura T., Sato N., Sato T., Hirabayashi J., Ikehara Y., et. al.
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 15829-15834
  • Peer Reviewed
• [Journal Article] Glycophorin A knockout mice, which lost sialoglycoproteins from the red blood cell membrane, are resistant to lethal infection of Babesia rodhaini (2007)
  • Author(s): Takabatake N., Okamura M., Yokoyama N., Ikehara Y., Akimitsu N., Arimitsu N, Hamamoto H., Sekimizu K., Suzuki H., and Igarashi I.
  • Journal Title: Veterinary Parasitology 148 Pages: 93-101
  • Peer Reviewed
• [Journal Article] Solitary bone metastasis as the first clinical manifestation in a patient with small bowel adenocarcinoma (2007)
  • Author(s): Yamada K, Ikehara Y., et. al.
  • Journal Title: J Orthop Sci. 12 Pages: 606-610
  • NAID: 10019995588
  • Peer Reviewed
• [Presentation] New treatment method for intra-abdominal metastasis, using carbohydrate recognition of macrophage (2008)
  • Author(s): 池原譲
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 糖鎖認識を介した感染メカニズムの解明と治療への利用の試み (2008)
  • Author(s): 池原譲
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle (2008)
  • Author(s): Ikehara, Y.
  • Organizer: American Association of Cancer Research, Annual meeting 2008
  • Place of Presentation: San Diego, California
• [Presentation] 糖鎖認識を介した感染メカニズムの解明と治療への利用の試み (2008)
  • Author(s): 池原譲
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 石川県金沢市
• [Presentation] New treatment method for intra-abdominal metastasis, using carbohydrate recognition of macrophage (2008)
  • Author(s): 池原譲
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 愛知県名古屋市
• [Presentation] Cancer vaccine delivery system using oligomannose coated liposomes (2007)
  • Author(s): Ikehara, Y., et. al.
  • Organizer: American Society of Glycobiology
  • Place of Presentation: Boston, USA
  • Year and Date: 2007-11-15
• [Presentation] A novel carbohydrate recognition-based drug delivery system to intraperit oneal metastases (2007)
  • Author(s): Ikehara, Y., et. al.
  • Organizer: Digestive Disease Week
  • Place of Presentation: Washington D.C, USA
  • Year and Date: 2007-05-20
• [Presentation] A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle American Association of Cancer Research
  • Author(s): Ikehara, Y., et al
  • Organizer: Annual meeting 2008
  • Place of Presentation: San Diego, USA
• [Presentation] Cancer vaccine delivery system using oligomannose coated liposomes
  • Author(s): Ikehara, Y., et al
  • Organizer: American Society of Glycobiology 2007
  • Place of Presentation: Boston, USA
• [Presentation] A novel carbohydrate recognition-based drug delivery system to intraperitoneal metastases
  • Author(s): Ikehara, Y., et al
  • Organizer: Digestive Disease Week 2007
  • Place of Presentation: Washington D.C, USA
• [Book] がん転移研究の実験手法 (2008)
  • Author(s): 池原譲, 済木育夫( 編さん)
  • Publisher: 金芳堂
• [Book] 遺伝子医学MOOK11 号「臨床糖鎖バイオマーカーの開発‐糖鎖機能の解明とその応用」
  • Author(s): 池原譲, 中西速夫
  • Publisher: メディカルドウ
• [Book] 遺伝子医学MOOK11 号「臨床糖鎖バイオマーカーの開発‐糖鎖機能の解明とその応用」
  • Author(s): 中西速夫, 池原譲
  • Publisher: メディカルドウ