SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ikuta, Y. Articles by Shiku, H. Search for Related Content PubMed PubMed Citation Articles by Ikuta, Y. Articles by Shiku, H. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3717-3724 IMMUNOBIOLOGY 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 Yasushi Ikuta, Naoyuki Katayama, Lijie Wang, Toshiharu Okugawa, Yoshiyuki Takahashi, Michael Schmitt, Xiaogang Gu, Masato Watanabe, Kazunari Akiyoshi, Hideo Nakamura, Kagemasa Kuribayashi, Junzo Sunamoto, and 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. 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. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kitano, S. Kageyama, Y. Nagata, Y. Miyahara, A. Hiasa, H. Naota, S. Okumura, H. Imai, T. Shiraishi, M. Masuya, et al. HER2-Specific T-Cell Immune Responses in Patients Vaccinated with Truncated HER2 Protein Complexed with Nanogels of Cholesteryl Pullulan Clin. Cancer Res., December 15, 2006; 12(24): 7397 - 7405. [Abstract] [Full Text] [PDF] S.-I. Sawada, Y. Nomura, Y. Aoyama, and K. Akiyoshi Heat Shock Protein-like Activity of a Nanogel Artificial Chaperone for Citrate Synthase Journal of Bioactive and Compatible Polymers, November 1, 2006; 21(6): 487 - 501. [Abstract] [PDF] K. Hasegawa, Y. Noguchi, F. Koizumi, A. Uenaka, M. Tanaka, M. Shimono, H. Nakamura, H. Shiku, S. Gnjatic, R. Murphy, et al. In vitro Stimulation of CD8 and CD4 T Cells by Dendritic Cells Loaded with a Complex of Cholesterol-Bearing Hydrophobized Pullulan and NY-ESO-1 Protein: Identification of a New HLA-DR15-Binding CD4 T-Cell Epitope Clin. Cancer Res., March 15, 2006; 12(6): 1921 - 1927. [Abstract] [Full Text] [PDF] N. Hoshino, N. Katayama, T. Shibasaki, K. Ohishi, J. Nishioka, M. Masuya, Y. Miyahara, M. Hayashida, D. Shimomura, T. Kato, et al. A novel role for Notch ligand Delta-1 as a regulator of human Langerhans cell development from blood monocytes J. Leukoc. Biol., October 1, 2005; 78(4): 921 - 929. [Abstract] [Full Text] [PDF] Y. Sakai, B. J. Morrison, J. D. Burke, J.-M. Park, M. Terabe, J. E. Janik, G. Forni, J. A. Berzofsky, and J. C. Morris Vaccination by Genetically Modified Dendritic Cells Expressing a Truncated neu Oncogene Prevents Development of Breast Cancer in Transgenic Mice Cancer Res., November 1, 2004; 64(21): 8022 - 8028. [Abstract] [Full Text] [PDF] V. Renard, L. Sonderbye, K. Ebbehoj, P. B. Rasmussen, K. Gregorius, T. Gottschalk, S. Mouritsen, A. Gautam, and D. R. Leach HER-2 DNA and Protein Vaccines Containing Potent Th Cell Epitopes Induce Distinct Protective and Therapeutic Antitumor Responses in HER-2 Transgenic Mice J. Immunol., August 1, 2003; 171(3): 1588 - 1595. [Abstract] [Full Text] [PDF] S. Gnjatic, D. Atanackovic, E. Jager, M. Matsuo, A. Selvakumar, N. K. Altorki, R. G. Maki, B. Dupont, G. Ritter, Y.-T. Chen, et al. Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses PNAS, July 22, 2003; 100(15): 8862 - 8867. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020