Proliferation Potential-Related Protein, an Ideal Esophageal Cancer Antigen for Immunotherapy, Identified Using Complementary DNA Microarray Analysis

  • Yoshihiro Yoshitake
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Tetsuya Nakatsura
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Mikio Monji
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Satoru Senju
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Hidetake Matsuyoshi
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Hirotake Tsukamoto
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Seiji Hosaka
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Hiroyuki Komori
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Daiki Fukuma
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Yoshiaki Ikuta
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;
  • Toyomasa Katagiri
    3Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan
  • Yoichi Furukawa
    3Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan
  • Hiromi Ito
    2Department of Oral and Maxillo Facial Surgery, Kumamoto University School of Medicine, Kumamoto; and
  • Masanori Shinohara
    2Department of Oral and Maxillo Facial Surgery, Kumamoto University School of Medicine, Kumamoto; and
  • Yusuke Nakamura
    3Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan
  • Yasuharu Nishimura
    1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto;

説明

<jats:title>Abstract</jats:title><jats:p>Purpose: To establish effective antitumor immunotherapy for esophageal cancer, we tried to identify an useful target antigen of esophageal cancer.</jats:p><jats:p>Experimental Design: We did cDNA microarray analysis to find a novel candidate antigen, proliferation potential-related protein (PP-RP). We examined cytotoxicity against tumor cells in vitro and in vivo of CTLs specific to PP-RP established from esophageal cancer patients.</jats:p><jats:p>Results: In 26 esophageal cancer tissues, an average of relative ratio of the expression of the PP-RP mRNA in cancer cells versus adjacent normal esophageal tissues was 396.2. Immunohistochemical analysis revealed that, in 20 of the 22 esophageal cancer tissues, PP-RP protein was strongly expressed only in the cancer cells and not so in normal esophageal epithelial cells. PP-RP protein contains 10 epitopes recognized by HLA-A24–restricted CTLs. These CTLs, generated from HLA-A24–positive esophageal cancer patients, had cytotoxic activity against cancer cell lines positive for both PP-RP and HLA-A24. Furthermore, adoptive transfer of the PP-RP–specific CTL line inhibited the growth of a human esophageal cancer cell line engrafted in nude mice.</jats:p><jats:p>Conclusions: The expression of PP-RP in esophageal cancer cells was significantly higher than in normal cells, and the CTLs recognizing PP-RP killed tumor cells in vitro and also showed tumor rejection effects in a xenograft model. Therefore, PP-RP may prove to be an ideal tumor antigen useful for diagnosis and immunotherapy for patients with esophageal cancer. cDNA microarray analysis is a useful method to identify ideal tumor-associated antigens.</jats:p>

収録刊行物

  • Clinical Cancer Research

    Clinical Cancer Research 10 (19), 6437-6448, 2004-10-01

    American Association for Cancer Research (AACR)

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