Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer§

Authors

  • Yi Li,

    1. Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
    2. Department of Gynecology and Obstetrics, Peking University People's Hospital, Beijing, People's Republic of China
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  • Hui Zeng,

    1. UConn Stem Cell Institute, and University of Connecticut School of Medicine, Farmington, Connecticut, USA
    2. Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
    3. Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China
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  • Ren-He Xu,

    1. UConn Stem Cell Institute, and University of Connecticut School of Medicine, Farmington, Connecticut, USA
    2. Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
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  • Bei Liu,

    Corresponding author
    1. Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
    2. UConn Stem Cell Institute, and University of Connecticut School of Medicine, Farmington, Connecticut, USA
    • Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA
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    • Telephone: +1-860-679-7979; Fax: +1-860-679-8130

  • Zihai Li

    Corresponding author
    1. Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
    2. UConn Stem Cell Institute, and University of Connecticut School of Medicine, Farmington, Connecticut, USA
    • Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA
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    • Telephone: +1-860-679-7979; Fax: +1-860-679-8130


  • Author contributions: Y.L.: collection and/or assembly of data, data analysis and interpretation; manuscript writing; H.Z.: generation, maintenance, and characterization of stem cells, manuscript writing; R.-H.X.: data analysis and interpretation, provision of study material, financial support, final approval of manuscript; B.L.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing; Z.L.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.

  • First published online in STEM CELLS EXPRESS October 8, 2009.

  • §

    Disclosure of potential conflicts of interest is found at the end of this article.

Abstract

The history of immunizing with embryonic materials to generate an antitumor immune response dates back to a century ago. The premise is that cancer cells share the expression of oncofetal antigens with embryonic materials and that the immune response against these antigens in the embryonic tissues is cross-protective against cancer. However, such a practice has never advanced beyond experimental animal settings, because of lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask whether tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated whether vaccination with defined human embryonic stem cells (hESCs) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hESC line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon-γ-producing cells and the profound loss of CD11b+Gr-1+ myeloid-derived suppressor cells in the spleen. No evidence of autoimmunity was observed. We also compared the immunogenicity against colon cancer between a hESC line CT2 and an iPS cell line TZ1 that were generated in the same stem cell facility. We found that the iPS cell line was inferior to the hESC line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hESCs and iPS cells. We conclude that the hESC-based vaccine is a promising modality for immunotherapy of cancer. STEM CELLS 2009;27:3103–3111

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