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2009 Fiscal Year Annual Research Report

新しい腫瘍抗原同定に基づく免疫療法の開発

Research Project

Project/Area Number 17016070
Research InstitutionKeio University

Principal Investigator

河上 裕  Keio University, 医学部, 教授 (50161287)

Co-Investigator(Kenkyū-buntansha) 藤田 知信  , 医学部, 助教 (20199334)
桜井 敏晴  , 医学部, 助教 (20101933)
工藤 千恵  , 医学部, 講師 (90424126)
塚本 信夫  , 医学部, 助教 (20407117)
植田 良  , 医学部, 助教 (30317143)
Keywords悪性黒色腫 / がん幹細胞 / 免疫療法 / 腫瘍抗原 / 免疫抵抗性
Research Abstract

本年度は、ヒトがん幹細胞(がん始原細胞)の免疫学的意義を検討した。ヒトグリオーマ患者血清を用いて、cDNAクローニング法で単離同定した脳腫瘍抗原は、グリオーマ組織からスフェアー形成法で樹立した細胞分画での発現が認められた。この細胞分画は免疫不全マウスへの移植により、患者脳腫瘍組織と同様な神経細胞とグリア細胞とより未熟な細胞の不均一な細胞群からなる腫瘍組織を形成し、グリオーマ幹細胞であると考えられた。このグリオーマ幹細胞は、脳腫瘍抗原特異的CTLにより傷害されたので、本腫瘍抗原は、グリオーマ幹細胞を排除し得る抗原として、免疫療法に有用である可能性が示唆された。しかし、これは培養細胞であるので、今後、in vivo非培養グリオーマ幹細胞へのT細胞による傷害性を検討する必要がある。また、ヒト悪性黒色腫細胞株からside population法を用いて、免疫不全マウスへの移植において、少数細胞で高い腫瘍形成能を示し、ABC-G2高発現、化学療法抵抗性というがん幹細胞様性質をもつ細胞分画を樹立した。この細胞分画の網羅的遺伝子発現解析により、悪性黒色腫幹細胞様細胞が発現する新規癌精巣抗原を同定した。悪性黒色腫における培養T細胞を用いた養子免疫療法で完全寛解後、数年後に再発を繰り返した症例を経験し、本症例では、免疫療法抵抗性の休止期悪性黒色腫細胞の存在、すなわち、がん幹細胞の存在が示唆された。上記悪性黒色腫幹細胞様細胞は、in vitro NK細胞傷害アッセイにおいて抵抗性をもつことが判明し、がん幹細胞は化学療法抵抗性だけでなく、免疫療法抵抗性である場合があることが示唆された。今後、この抵抗性の分子機構を解明する必要がある。

  • Research Products

    (23 results)

All 2010 2009

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (9 results) Book (2 results)

  • [Journal Article] Identification of HLA-A2- and A24-restricted T-cell epitopes derived from SOX6 expressed in glioma stem cells for immunotherapy.2010

    • Author(s)
      Ueda R, et al.
    • Journal Title

      Int J Cancer. 126(4)

      Pages: 919-929

    • Peer Reviewed
  • [Journal Article] Aberrant Fatty Acid-Binding Protein 7 Gene Expression In Cutaneous Malignant Melanoma.2010

    • Author(s)
      Goto Y, et al.
    • Journal Title

      J Invest Dermatol. 130(1)

      Pages: 221-229

    • Peer Reviewed
  • [Journal Article] Isolation of cancer stem-like cells from a side population of a humanglioblastoma cell line, SK-MG-1.2010

    • Author(s)
      Fukaya R, et al.
    • Journal Title

      Cancer Letters. 291(2)

      Pages: 150-157

    • Peer Reviewed
  • [Journal Article] Adjuvant effects of formalin-inactivated HSV through activation of dendritic cells and inactivation of myeloid-derived suppressor cells in cancer immunotherapy.2010

    • Author(s)
      Ohkusu-Tsukada K, et al.
    • Journal Title

      Int J Cancer. (in press)

    • Peer Reviewed
  • [Journal Article] Targeted inhibition of the p38 MAP kinase of IL-10-secreting CD25- Tregulatory cells in cancer immunotherapy.2010

    • Author(s)
      Ohkusu-Tsukada K, et al.
    • Journal Title

      Eur.J Immunol. 40(4)

      Pages: 1011-1021

    • Peer Reviewed
  • [Journal Article] Impairment of pDC for IFN production by the ligand forimmunoglobulin-like transcript 7 (ILT7) expressed on human cancer cells.2009

    • Author(s)
      Tsukamoto N, et al.
    • Journal Title

      Clin Cancer Res. 15(18)

      Pages: 5733-5743

    • Peer Reviewed
  • [Journal Article] Simultaneous suppression of MITF and BRAFV600E enhanced inhibition of melanoma cell proliferation.2009

    • Author(s)
      Kido K, et al.
    • Journal Title

      Cancer Sci. 100(10)

      Pages: 1863-1869

    • Peer Reviewed
  • [Journal Article] RNA Helicase Encoded by Melanoma Differentiation-Associated Gene 5 Is a Major Autoantigen in Patients With Clinically Amyopathic Dermatomyositis.2009

    • Author(s)
      Sato S, et al.
    • Journal Title

      Arthritis Rheum. 60(7)

      Pages: 2193-2200

    • Peer Reviewed
  • [Journal Article] Activation of dendritic-like cells and neural stem/progenitor cells in injured spinal cord by GM-CSF.2009

    • Author(s)
      Hayashi K, et al.
    • Journal Title

      Neurosci Res. 64(1)

      Pages: 96-103

    • Peer Reviewed
  • [Journal Article] Transplantation of dendritic cells promotes functional recovery from spinalcord injury in common marmoset.2009

    • Author(s)
      Yaguchi M, et al.
    • Journal Title

      Neurosci Res. 654

      Pages: 384-392

    • Peer Reviewed
  • [Journal Article] Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease.2009

    • Author(s)
      Ogawa Y, et al.
    • Journal Title

      Am J Pathol. 175(6)

      Pages: 2372-2381

    • Peer Reviewed
  • [Journal Article] Emerging concepts in biomarker discovery.2009

    • Author(s)
      Tahara H., et al.
    • Journal Title

      the US-Japan Workshop on Immunological Molecular Markers in Oncology.J Transl Med. 7

      Pages: 45

    • Peer Reviewed
  • [Presentation] Improvement of immunotherapy by restoration of immunocompetence through targeting signaling molecules in cancer and immune cells.2010

    • Author(s)
      Yutaka Kawakami.
    • Organizer
      8th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
    • Place of Presentation
      Hilton Waikoloa Village Waikoloa, Hawaii, USA.
    • Year and Date
      2010-02-06
  • [Presentation] MIF acts as a direct regulator of P53 in glioma cells and is a novelmolecular target for glioma cancer stem cells.2009

    • Author(s)
      Fukaya R, et al.
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-11
  • [Presentation] Generation of human melanocytes from iPS cells in vitro.2009

    • Author(s)
      Ohta S, et al.
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-10
  • [Presentation] Promotion of cancer metastasis through immuno-suppression and-resistance induced by Snail induced EMT.2009

    • Author(s)
      Kawakami Yutaka.
    • Organizer
      Japanses-German Cancer Workshop
    • Place of Presentation
      Germany
    • Year and Date
      2009-09-17
  • [Presentation] Development of cancer immunotherapy through molecular analyses on anti-tumor immune responses.2009

    • Author(s)
      Kawakami Y, et al.
    • Organizer
      Intemational Symposium of novel therapies for unresectable cancers(ISNTUC)
    • Place of Presentation
      Sheraton Dameisha Resort Hotel
    • Year and Date
      2009-08-09
  • [Presentation] Inhibition of a MAPK signal in cancer cells enhanced specificanti-tumor immunity by increased production of chemokines.2009

    • Author(s)
      Iwata-Kajihara T, et al.
    • Organizer
      第15回日本遺伝子治療学会総会
    • Place of Presentation
      大阪大学コンベンションセンター
    • Year and Date
      2009-07-10
  • [Presentation] STK24 is a signaling molecule for cancer-induced immunosuppression through IL-10 and TGF-β 1 production.2009

    • Author(s)
      Kawamura N, et al.
    • Organizer
      第15回日本遺伝子治療学会総会
    • Place of Presentation
      大阪大学コンベンションセンター
    • Year and Date
      2009-07-10
  • [Presentation] MIF acts as a direct regulator of P53 in the nuclei of glioma cells and is a novel molecular target for the treatment of glioma cancerstem cells.2009

    • Author(s)
      Fukaya R, et al.
    • Organizer
      7th International Society for Stem Cell Research, Annual Meeting
    • Place of Presentation
      Centre Convencions international Barcelona, Carcelona, Spain
    • Year and Date
      2009-07-09
  • [Presentation] Immunoescape of cancer cells expressing an endogenous retrovirus antigen.2009

    • Author(s)
      Kudo-Saito C, et al.
    • Organizer
      100th Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Denver, (USA)
    • Year and Date
      2009-04-21
  • [Book] Wang RF ed, Springer Science/Business Media, New York USA2010

    • Author(s)
      Ueda R, Kawakami Y.
    • Publisher
      Human tumor antigens recognized by T cells and their implications for cancer immunotherapy in "Innate and adaptive immuneregulation and Cancer immunotherapy"(in press)
  • [Book] Humana Press2009

    • Author(s)
      Sumimoto H, Kawakami Y.
    • Total Pages
      187-199
    • Publisher
      The RNA silencing technology applied by lentiviral vectors in oncology, in "Lentivirus Gene Engineering Protocols second edition"

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Published: 2011-06-16   Modified: 2016-04-21  

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