Presentation of a major histocompatibility complex class 1–binding peptide by monocyte-derived dendritic cells incorporating hydrophobized polysaccharide–truncated HER2 protein complex: implications for a polyvalent immuno-cell therapy

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  • Yasushi Ikuta
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Naoyuki Katayama
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Lijie Wang
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Toshiharu Okugawa
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Yoshiyuki Takahashi
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Michael Schmitt
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Xiaogang Gu
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Masato Watanabe
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Kazunari Akiyoshi
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Hideo Nakamura
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Kagemasa Kuribayashi
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Junzo Sunamoto
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.
  • Hiroshi Shiku
    From the Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, and the Department of Bioregulation, Mie University School of Medicine, Tsu; the First Department of Surgery, Nagasaki University School of Medicine; the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University; and the Yokohama Research Center, Tokyo-Mitsubishi, Kanagawa, Japan.

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Abstract

<jats:p>Recognition of the essential role of dendritic cells (DCs) as professional antigen-presenting cells has prompted investigators to search for methods to use DCs as natural adjuvants in immunotherapy. A number of antigenic oligopeptides, recognized by CD8+cytotoxic T lymphocytes (CTLs) specific for cancer cells, have been applied in clinical trials using DCs. Such a monovalent vaccine with a single epitope for a particular type of HLA class 1 molecule would be effective. However, a polyvalent vaccine might be more potent. We designed a novel protein delivery system consisting of hydrophobized polysaccharides complexed with target proteins. The truncated HER2 protein encompassing 147 N-terminal amino acids, including the 9-mer HER2p63-71 peptide (HER2p63), TYLPTNASL, the human homologue of an antigenic murine tumor rejection peptide, was prepared. We report here that HLA-A2402+ DCs could incorporate hydrophobized polysaccharide–truncated HER2 protein complexes and process the protein to present major histocompatibility complex class 1-binding HER2p63 peptide. The complexes enter DCs by phagocytosis, and then the truncated protein is processed through a pathway similar to that for endogenous proteins. DCs sensitized by these complexes primed and boosted HER2p63-specific CD8+T cells in the context of HLA-A2402. Vaccination with DCs incorporating these complexes completely suppressed lung metastases in a HER2-expressing murine tumor model. We also generated 3 CD4+ clones reactive with different HER2- derived 25-mer peptides from lymph node cells in mice treated with CHP/HER2-147. Thus, hydrophobized polysaccharide–protein complexes are promising candidates for the construction of polyvalent vaccines.</jats:p>

Journal

  • Blood

    Blood 99 (10), 3717-3724, 2002-05-15

    American Society of Hematology

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