Identification of SPARC as a candidate target antigen for immunotherapy of various cancers

Authors

  • Mitsuhiro Inoue,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    2. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Satoru Senju,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Shinya Hirata,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Yoshiaki Ikuta,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    2. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Yuki Hayashida,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Atsushi Irie,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Michiko Harao,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    2. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Katsunori Imai,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Yusuke Tomita,

    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Takuya Tsunoda,

    1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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  • Yoichi Furukawa,

    1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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  • Takaaki Ito,

    1. Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Yusuke Nakamura,

    1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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  • Hideo Baba,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Yasuharu Nishimura

    Corresponding author
    1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    • Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan
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    • Fax: +[81-96-373-5314]


Abstract

To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2Kd-restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2Kd-binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1143–151 (DYIGPCKYI) and SPARC-A24-4225–234 (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy.

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