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2008 Fiscal Year Final Research Report

Development of effective immunotherapy by combining methods to restore immunocompetence of cancer patients

Research Project

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Project/Area Number 19390355
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKeio University

Principal Investigator

KAWAKAMI Yutaka  Keio University, 医学部, 教授 (50161287)

Co-Investigator(Kenkyū-buntansha) KITAGAWA Yuukou  慶應義塾大学, 医学部, 教授 (20204878)
FUJITA Tomonobu  慶應義塾大学, 医学部, 助教 (20199334)
SAKURAI Toshiharu  慶應義塾大学, 医学部, 助教 (20101933)
TSUKAMOTO Nobuo  慶應義塾大学, 医学部, 助教 (20407117)
KUDO Chie  慶應義塾大学, 医学部, 助教 (90424126)
SUMIMOTO Hidetoshi  慶應義塾大学, 医学部, 助教 (00306838)
Project Period (FY) 2007 – 2008
Keywords大腸癌 / 免疫療法 / 免疫抑制 / 樹状細胞 / シグナル伝達阻害 / 上皮間葉転換
Research Abstract

本研究では、効果的な免疫療法の開発のために、消化器癌による免疫抑制の分子機構の解明と克服法の開発、および免疫療法の標的となるヒト消化器癌抗原の同定を試みた。その結果、発現と良好な予後との相関がみられ、免疫原性の高い腫瘍抗原が同定され、さらに、大腸癌シグナル異常による免疫抑制機構が明らかになり、in vitroおよび大腸癌マウスモデルで、シグナル阻害による免疫抑制の解除と免疫療法の効果増強の可能性が示された。

  • Research Products

    (52 results)

All 2009 2008 2007 Other

All Journal Article (12 results) (of which Peer Reviewed: 11 results) Presentation (36 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Cancer metastasis is accelerated through immunosuppression during EMT of cancer cell2009

    • Author(s)
      Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y.
    • Journal Title

      Cancer Cell 16

      Pages: 195-206

    • Peer Reviewed
  • [Journal Article] A Pilot Study of Human Interferon β Gene Therapy for Patients with Advanced Melanoma by in vivo Transduction Using Cationic Liposomes2008

    • Author(s)
      Matsumoto K, Kubo H, Murata H, Uhara H, Takata M, Shinichi Shibata S, Yasue S, Sakakibara A, Yasushi TomitaY, Toshiro Kageshita T, Kawakami Y, Mizuno M, Yoshida J and Saida T.
    • Journal Title

      Jpn J Clin Oncol 38

      Pages: 849-856

    • Peer Reviewed
  • [Journal Article] Identification of a WT1 protein-derived peptide, WT1, as a HLA-A 0206-restricted, WT1-specific CTL epitope2008

    • Author(s)
      Li Z, Oka Y, Tsuboi A, Fujiki F, Harada Y, Nakajima H, Masuda T, Fukuda Y, Kawakatsu M, Morimoto S, Katagiri T, Tatsumi N, Hosenn N, Shirakata T, Nishida S, Kawakami Y, Udaka K, Kawase I, Oji Y, Sugiyama H.
    • Journal Title

      Microbiol Immunol 52

      Pages: 551-558

    • Peer Reviewed
  • [Journal Article] Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX62008

    • Author(s)
      Ueda R, Kinoshita E, Ito R, Kawase T, Kawakami Y, Toda M.
    • Journal Title

      Int J Cancer 122

      Pages: 2274-2279

    • Peer Reviewed
  • [Journal Article] Isolation and characterization of dendritic cells from common marmosets for preclinical studies on cell therapy2008

    • Author(s)
      Ohta S, Ueda Y, Yaguchi M, Matsuzaki Y, Nakamura M, Toyama Y, Tanioka Y, Tamaoki N, Nomura T, Okano H, Kawakami Y, Toda M.
    • Journal Title

      Immunol 123

      Pages: 566-574

    • Peer Reviewed
  • [Journal Article] Dendritic cell based personalized immunotherapy based on cancer antigen research2008

    • Author(s)
      Kawakami Y, Fujita T, Kudo C, Sakurai T, Udagawa M, Yaguchi T, Hasegawa G, Hayashi E, Ueda Y, Iwata T, Wang Q, Okada S, Tsukamoto N, Matsuzaki Y, Sumimoto H.
    • Journal Title

      Frontier in Bioscience 13

      Pages: 1952-1958

    • Peer Reviewed
  • [Journal Article] Lentiviral Vector-Mediated RNAi and it's use for Cancer Research2007

    • Author(s)
      Sumimoto H, Kawakami Y.
    • Journal Title

      Future Oncology 3

      Pages: 655-664

    • Peer Reviewed
  • [Journal Article] Identification of a novel cancer-testis antigen CRT2 frequently expressed in various cancers using representational differential analysis2007

    • Author(s)
      Hayashi E, Matsuzaki Y, Kurihara S, Hasegawa G, Fujita T, Yaguchi T, Kageshita T, Sano M, Kawakami Y.
    • Journal Title

      Clin Cancer Res. 13

      Pages: 6267-6274

    • Peer Reviewed
  • [Journal Article] Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis2007

    • Author(s)
      Yoshizawa S, Matsuoka K, Inoue N, Takaishi H, Ogata H, Iwao Y, Mukai M, Fujita T, Kawakami Y, Hibi T.
    • Journal Title

      Inflamm Bowel Dis.13

      Pages: 865-873

    • Peer Reviewed
  • [Journal Article] Toda M. Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients2007

    • Author(s)
      Ueda R, Yoshida K, Kawase T, Kawakami Y, Toda M.
    • Journal Title

      Int J Cancer 120

      Pages: 1704-1711

    • Peer Reviewed
  • [Journal Article] Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-cell lymphoma2007

    • Author(s)
      Inozume T, Mitsui H, Okamoto T, Matsuzaki Y, Kawakami Y, Shibagaki N, Shimada S.
    • Journal Title

      J Invest Dermatol 127

      Pages: 2818-2822

    • Peer Reviewed
  • [Journal Article] Development of individualized immunotherapy based on the analysis on anti-tumor immune responses to the human tumor antigens identified using immunological and genetic methods2007

    • Author(s)
      Kawakami Y, Fujita T, Kudo C, Sakurai T, Udagawa M, Hasegawa G, Ishida A, Kitagawa Y, Tanabe M, Saito M, Izumi Y, Kawamura M, Yaguchi T, Ueda Y, Hayashi E, Wang Q, Tsukamoto N, Matsuzaki Y, Sumimoto H, Takeuchi H, Tanikawa A, Handa M, Amagai M, Kobayashi K, Ikeda Y, Azuma I, and Kitajima M.
    • Journal Title

      Gene Therapy

      Pages: 240-248

  • [Presentation] 消化器癌に対する樹状細胞を腫瘍内投与による免疫療法の第I相臨床試験2008

    • Author(s)
      藤田知信、田邉稔、北川雄光、石田明、桜井敏晴、半田誠、北島政樹、河上裕
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
  • [Presentation] 癌細胞におけるMAPKシグナル亢進による腫瘍免疫逃避機構の解明2008

    • Author(s)
      谷口智憲、木藤健治、塚本信夫、桜井敏晴、藤田知信、持丸博史、丸山正太郎、里見良輔、井田陽介、住本秀敏、河上裕
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
  • [Presentation] 上皮-間葉転換期にある癌細胞から高産生されるIL-13を介した樹状細胞の機能阻害2008

    • Author(s)
      工藤千恵、河上裕
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
  • [Presentation] Application of tumor cryoablation in the development of cancer immunorherapy2008

    • Author(s)
      Kawakami Y
    • Organizer
      第35回日本低温医学会総会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-23
  • [Presentation] Molecular mechanisms for generation of immunosuppressive microenvironment by cancer cells2008

    • Author(s)
      Kawakami Y
    • Organizer
      International Society for Biological Therapy of Cancer
    • Place of Presentation
      CA(USA)
    • Year and Date
      2008-11-01
  • [Presentation] 大腸癌新規診断マーカーとしてのKU-CR4の同定2008

    • Author(s)
      塚本信夫、寺本華菜、岡田勉、大浪陽子、井田陽介、河上裕
    • Organizer
      第67回日本癌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
  • [Presentation] 上皮-間葉転換期にある癌細胞が転移能獲得と共に誘導する免疫抑制ならびにその制御2008

    • Author(s)
      工藤千恵、河上裕
    • Organizer
      第67回日本癌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
  • [Presentation] 癌細胞の転移と抗腫瘍免疫回避に密接に関与する内因性レトロウィルス抗原の発現2008

    • Author(s)
      山本隆介、由良昌大、河上裕、工藤千恵
    • Organizer
      第67回日本癌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
  • [Presentation] 培養樹状細胞を用いた免疫療法2008

    • Author(s)
      河上裕、住本秀敏、工藤千恵、塚本信夫、藤田知信、桜井敏晴、谷口智憲、岩田知子、川村直
    • Organizer
      第67回日本癌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
  • [Presentation] Immunotherapy by intratumoral administration of dendritic cells following cryoablative tumor treatment2008

    • Author(s)
      河上裕
    • Organizer
      第36回日本臨床免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-17
  • [Presentation] Immunotherapy by intratumoral administration of BCG-CWS treated DC following cryoablative tumor pretreatment2008

    • Author(s)
      Kawakami Y
    • Organizer
      10^<th> International Symposium on Dendritic Cells
    • Place of Presentation
      神戸
    • Year and Date
      2008-10-03
  • [Presentation] Tumor Immunotherapy2008

    • Author(s)
      Kawakami Y
    • Organizer
      国際シンポジウム生体の「事態」をめぐって「生命の維持、破綻と再生、免疫・移植・癌・感染・幹細胞」
    • Place of Presentation
      東京
    • Year and Date
      2008-09-20
  • [Presentation] Cancer metastasis is accelerated through immunosuppression during epithelialmesenchymal transition of cancer cells2008

    • Author(s)
      工藤千恵、竹内直志、河上裕
    • Organizer
      第12回基盤的癌免疫研究会
    • Place of Presentation
      埼玉
    • Year and Date
      2008-07-03
  • [Presentation] より有効な細胞障害性T細胞誘導を目指して2008

    • Author(s)
      河上裕
    • Organizer
      第32回日本リンパ学会総会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-07
  • [Presentation] Immunosuppressive mechanisms induced by tumor cells during epithelial-mesenchymal transition leading to tumor metastasis2008

    • Author(s)
      Kudo-Saito C, Shirako H, Kawakami Y
    • Organizer
      99^<th> Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      CA(USA)
    • Year and Date
      2008-04-14
  • [Presentation] Use of RNA interference for analysis of anti-cancer immune responses and development of immunotherapy2008

    • Author(s)
      Kawakami Y
    • Organizer
      The Avison Biomedical Symposium
    • Place of Presentation
      Seoul(Korea)
    • Year and Date
      2008-01-17
  • [Presentation] Molecular mechanisms for generation of immunosuppressive microenvironment by cancer cells2007

    • Author(s)
      Kawakami Y, Hidetoshi Sumimoto, Chie Kudo, Tomonori Yaguchi
    • Organizer
      第37回日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
  • [Presentation] ホルマリン加工したHSVアジュバントのミエロイド・サプレッサー細胞の蓄積抑制による抗腫瘍効果2007

    • Author(s)
      Ohkusu-Tsukada K, Ohta S, Kawakami Y, Masahiro Toda
    • Organizer
      第37回日本免疫学会総
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
  • [Presentation] Induction of FoxP3(+)regulatory T cells by colon cancer cells during epithelial-mesenchymal transition2007

    • Author(s)
      Kudo C, Oike M, Kawakami Y
    • Organizer
      第37回日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
  • [Presentation] Possible mechanism of metastasis enhancement of tumors during epithelial-mesenchymal transition by mediating via immunosuppression involving regulatory T cells2007

    • Author(s)
      Takeuchi T, Kudo C, Kawakami Y
    • Organizer
      第37回日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
  • [Presentation] 癌細胞におけるimmunoglobulin-like transcript 7 (ILT7) リガンドの発現と免疫抑制2007

    • Author(s)
      Tsukamoto N, Okada S, Sasaki Y, Kawakami Y
    • Organizer
      第37回日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
  • [Presentation] Possible inhibition of TLR signaling by PI3K through preventing PIP2- associated TIRAP recruitment to plasma cell membrane in human dendritic cells2007

    • Author(s)
      Sumimoto H, Takahashi T, Kawakami Y
    • Organizer
      第37回日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-21
  • [Presentation] Immunotherapy by Intra-tumoral Administration of Dendritic Cells Following Cryoablative Tumor Treatment2007

    • Author(s)
      Kawakami Y
    • Organizer
      14th World congress of cryosurgery, International society of cryosurgery
    • Place of Presentation
      Beijing(China)
    • Year and Date
      2007-11-05
  • [Presentation] がん免疫療法の現状と展望2007

    • Author(s)
      河上裕
    • Organizer
      第12回北九州がんセミナー
    • Place of Presentation
      福岡
    • Year and Date
      2007-11-02
  • [Presentation] がん免疫療法の臨床試験実施における諸問題2007

    • Author(s)
      河上裕
    • Organizer
      第45回日本癌治療学会
    • Place of Presentation
      京都
    • Year and Date
      2007-10-24
  • [Presentation] Immunotherapy by intratumoral administration of dendritic cells2007

    • Author(s)
      Kawakami Y, Fujita T, Kudo C, Udagawa M, Sakurai T, Ueda Y, Yaguchi T, Sumimoto H
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
  • [Presentation] Immunosuppressive mechanisms induced by tumor cells during epithelial-mesenchymal transition2007

    • Author(s)
      Kudo C, Shirako H, Oike M, Tsukamoto N, Kawakami Y
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
  • [Presentation] BORIS is a possible marker for poor prognosis with distant metastasis in patients with colorectal cancer2007

    • Author(s)
      Fujita T, Hirao N, Okada T, Tsukamoto N, Okabayashi K, Kitagawa Y, Kitajima M, Kawakami Y
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
  • [Presentation] がんに対する免疫応答と免疫療法2007

    • Author(s)
      河上裕
    • Organizer
      第28回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Year and Date
      2007-08-03
  • [Presentation] 癌シグナル伝達異常による癌免疫逃避機構の解析2007

    • Author(s)
      谷口智憲、木藤健治、丸山正太郎、住本秀敏、河上裕
    • Organizer
      第28回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Year and Date
      2007-08-03
  • [Presentation] Immunoglobulin-like transcript 7(ILT7)リガンドの癌細胞株における発現2007

    • Author(s)
      塚本信夫、Okada S、佐々木雄亮、河上裕
    • Organizer
      第11回基盤的癌免疫研究会
    • Place of Presentation
      東京
    • Year and Date
      2007-07-11
  • [Presentation] Clinical significance of serum p53 antibodies in patients with ulcerative colitis2007

    • Author(s)
      Yoshizawa S, Matsuoka K, Inoue N, Takaishi H, Ogata H, Iwao Y, Mukai M, Fujita T, Kawakami Y, Hibi T
    • Organizer
      13^<th> International Congress of Mucosal Immunology
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-07-11
  • [Presentation] Enhancement of Human Monocyte-Derived Dendritic Cell Functions by Adenovirus-Mediated RNA Interference of STAT-32007

    • Author(s)
      Iwata T, Sumimoto H, Mizuguchi H, Kawakami Y
    • Organizer
      第13回日本遺伝子治療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-29
  • [Presentation] Immunotherapy and gene therapy using viral vectors2007

    • Author(s)
      Kawakami Y, Udagawa M , Kido K, Yaguchi T, Toda M, Kudo C, Sumimoto H
    • Organizer
      第13回日本遺伝子治療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-28
  • [Presentation] テーラーメイド医療と免疫治療2007

    • Author(s)
      河上裕
    • Organizer
      第27回日本医学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-08
  • [Presentation] 癌免疫療法 : 固形癌に対するT細胞・樹状細胞療法2007

    • Author(s)
      河上裕
    • Organizer
      第104回日本内科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-05
  • [Book] The RNA silencing technology applied by lentiviral vectors in oncology, in "Lentivirus Gene Engineering Protocols book the second edition"Humana Press

    • Author(s)
      Sumimoto H, and Kawakami Y.
    • Publisher
      Totowa, NJ.(in press)
  • [Remarks]

    • URL

      http://web.sc.itc.keio.ac.jp/admedres/index-jp.html

  • [Patent(Industrial Property Rights)] 腫瘍細胞による免疫抑制の解除剤とそれを用いた抗腫瘍剤2008

    • Inventor(s)
      工藤千恵、河上裕
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Number
      PCT/JP2008/064987
    • Filing Date
      2008-08-22
  • [Patent(Industrial Property Rights)] がんの診断方法と治療方法2008

    • Inventor(s)
      工藤千恵、河上裕
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Number
      特願2008-239943
    • Filing Date
      2008-09-18

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Published: 2010-06-10   Modified: 2016-04-21  

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