In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies

Authors

  • Xu-Dong Tang,

    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
    2. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
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    • These authors contributed equally to this study.
  • Shu-Liang Guo,

    1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
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    • These authors contributed equally to this study.
  • Guo-Zhen Wang,

    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
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  • Ning Li,

    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
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  • Yu-Yun Wu,

    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
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  • Dian-Chun Fang,

    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
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  • Ya-Han Fan,

    Corresponding author
    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
    • Ya-Han Fan and Shi-Ming Yang, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

      Tel: +86-132-2868-6589; Fax: +86-023-6875-5604;

      E-mails: shimingyang@yahoo.com; yahanfan@139.com

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  • Shi-Ming Yang

    Corresponding author
    1. Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
    2. Biomedical Analysis Center, Third Military Medical University, Chongqing, China
    3. Chongqing Key Laboratory for Diseases Proteomics, Southwest Hospital, Third Military Medical University, Chongqing, China
    • Ya-Han Fan and Shi-Ming Yang, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

      Tel: +86-132-2868-6589; Fax: +86-023-6875-5604;

      E-mails: shimingyang@yahoo.com; yahanfan@139.com

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Abstract

Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen. However, vaccine therapy targeting only one cytotoxic T lymphocyte (CTL) epitope is suboptimal in preventing cancer. In the present study, we designed heparanase multi-epitope vaccines to increase the immune response to standard single heparanase epitopes. The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo. Heparanase multi-epitope vaccines not only induced the heparanase-specific CTL to lyse tumor cells but also increased CTL secretion of interferon-γ. However, these heparanase-specific CTL did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirms the safety of these multi-epitope vaccines. Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.

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