Translational and Clinical Research

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

  1. Yi Li1,4,
  2. Hui Zeng2,3,5,
  3. Ren-He Xu2,3,
  4. Bei Liu1,2,¶,*,
  5. Zihai Li1,2,‖,*

Article first published online: 8 OCT 2009

DOI: 10.1002/stem.234

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 12, pages 3103–3111, December 2009

Additional Information

How to Cite

Li, Y., Zeng, H., Xu, R.-H., Liu, B. and Li, Z. (2009), Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer. STEM CELLS, 27: 3103–3111. doi: 10.1002/stem.234

Author Information

  1. 1

    Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

  2. 2

    UConn Stem Cell Institute, and University of Connecticut School of Medicine, Farmington, Connecticut, USA

  3. 3

    Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

  4. 4

    Department of Gynecology and Obstetrics, Peking University People's Hospital, Beijing, People's Republic of China

  5. 5

    Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China

  1. Telephone: +1-860-679-7979; Fax: +1-860-679-8130

  2. ‖

    Telephone: +1-860-679-7979; Fax: +1-860-679-8130

*Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA

  1. †

    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.

  2. ‡

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

  3. §

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

  4. Telephone: +1-860-679-7979; Fax: +1-860-679-8130

  5. ‖

    Telephone: +1-860-679-7979; Fax: +1-860-679-8130

Publication History

  1. Issue published online: 14 DEC 2009
  2. Article first published online: 8 OCT 2009
  3. Accepted manuscript online: 8 OCT 2009 12:00AM EST
  4. Manuscript Accepted: 23 SEP 2009
  5. Manuscript Received: 30 JUL 2009

Funded by

  • Connecticut Stem Cell Research Grants Program. Grant Numbers: 06SCA031, 06SCD02
  • University of Connecticut School of Medicine
  • Leukemia and Lymphoma Society

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Keywords:

  • Embryonic stem cells;
  • Induced pluripotent stem cells;
  • Cancer vaccine;
  • Oncofetal antigen;
  • Myeloid-derived suppressor cells

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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