HLA多型を考慮したがん免疫療法の開発  [in Japanese] Development of an Ideal and Potent Cancer Immunotherapy Designed by Consideration of HLA Polymorphism  [in Japanese]

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Author(s)

    • 冨田 雄介 Tomita Yusuke
    • 熊本大学大学院生命科学研究部呼吸器病態学分野|熊本大学大学院生命科学研究部免疫識別学分野 Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University|Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University
    • 千住 覚 Senju Satoru
    • 熊本大学大学院生命科学研究部免疫識別学分野 Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University
    • 入江 厚 Irie Atsushi
    • 熊本大学大学院生命科学研究部免疫識別学分野 Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University
    • 西村 泰治 Nishimura Yasuharu
    • 熊本大学大学院生命科学研究部免疫識別学分野 Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University

Abstract

がん細胞特異的に免疫応答を誘導するために,正常細胞には発現せず,がん細胞にのみ強く発現する腫瘍関連抗原(TAA; Tumor-associated antigen)の遺伝子を,ゲノムワイドcDNAマイクロアレイ解析により同定した。TAAのアミノ酸配列をもとに,日本人で頻度が高いHLA-A2あるいはA24に結合するペプチドを<i>in silico</i>で予測して合成し,HLAトランスジェニックマウスやヒト末梢血単核細胞をTAAペプチドで刺激することにより,当該HLA分子により提示されたTAAペプチドに特異的に反応し,がん細胞を殺す細胞傷害性T細胞(CTL)を誘導できるペプチドを同定した。これらを用いた,がん免疫療法の医師主導型第I 相臨床研究により,安全性が確認され奏効例も観察された。さらに,より有効ながん免疫療法の開発を目指して,CTLとヘルパーT(Th)細胞を同時に誘導できるTAAペプチドや,組織不適合性を回避できる遺伝子改変iPS細胞由来の樹状細胞を用いた細胞ワクチン療法の開発など,著者らの最近の研究成果について紹介する。

To develop cancer immunotherapy, we identified the tumor-associated antigens (TAAs) that are prominently expressed only in cancer cells but not in normal tissues by using the genome-wide cDNA microarray analyses. TAA-derived peptides predicted <i>in silico</i> to be bound by frequent HLA class I molecules in the Japanese population were synthesized, and several peptides that could induce the HLA class I-restricted, TAA peptide-specific and tumor-reactive cytotoxic T lymphocyte (CTL) were identified by using HLA class I transgenic mice and human peripheral blood mononuclear cells. The phase I clinical trials of cancer immunotherapy using those TAA-derived peptides showed the safety and some effectiveness. To further improve the effectiveness of the TAA-targeted cancer immunotherapy, we identified TAA-derived peptides that can stimulate both TAA-specific CTL and helper T (Th) cells, and developed genetically modified allogeneic iPS cell-derived dendritic cell-mediated immunotherapy that can overcome the potential problems of histoincompatibility between iPS cell donors and cancer patients.

Journal

  • Major Histocompatibility Complex

    Major Histocompatibility Complex 20(1), 45-56, 2013

    Japanese Society for Histocompatibility and Immunogenetics

Codes

  • NII Article ID (NAID)
    130004647538
  • Text Lang
    JPN
  • ISSN
    2186-9995
  • Data Source
    J-STAGE 
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