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Her-2 DNA versus cell vaccine: immunogenicity and anti-tumor activity

Cancer Immunology, Immunotherapy volume 58, pages 759–767 (2009)Cite this article

Abstract

Direct comparison and ranking of vaccine formulations in pre-clinical studies will expedite the identification of cancer vaccines for clinical trials. Two human ErbB-2 (Her-2) vaccines, naked DNA and whole cell vaccine, were tested side-by-side in wild type and Her-2 transgenic mice. Both vaccines can induce humoral and cellular immunity to the entire repertoire of Her-2 epitopes. Mice were electro-vaccinated i.m. with a mixture of pGM-CSF and pE2TM, the latter encodes Her-2 extracellular and transmembrane domains. Alternatively, mice were injected i.p. with human ovarian cancer SKOV3 cells that have amplified Her-2. In wild type mice, comparable levels of Her-2 antibodies (Ab) were induced by these two vaccines. However, T cell immunity and protection against Her-2+ tumors were superior in DNA vaccinated mice. In BALB Her-2 transgenic (Tg) mice, which were tolerant to Her-2, DNA and cell vaccines were administered after regulatory T cells (Treg) were removed by anti-CD25 mAb. Again, comparable levels of Her-2 Ab were induced, but DNA vaccines rendered greater anti-tumor activity. In B6xDR3 Her-2 Tg mice that expressed the autoimmune prone HLA-DR3 allele, higher levels of Her-2 Ab were induced by SKOV3 cell than by Her-2 DNA. But anti-tumor activity was still more profound in DNA vaccinated mice. Therefore, Her-2 DNA vaccine induced greater anti-tumor immunity than cell vaccine, whether mice were tolerant to Her-2 or susceptible to autoimmunity. Through such side-by-side comparisons in appropriate pre-clinical test systems, the more effective vaccine formulations will emerge as candidates for clinical trials.

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Acknowledgments

This study was supported by NIH CA76340, CA125680 (WZW), Department of Defense W81XWH-04-1-0546 (WZW) and GM 58905-7 (IMSD). The authors wish to thank David Shim and Andi Cani for their technical assistance. We also thank Serene Lane and Laura Baksic for their expert care of the experimental animals.

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Affiliations

  1. Department of Immunology and Microbiology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA

    Paula J. Whittington & Wei-Zen Wei

  2. Karmanos Cancer Institute, School of Medicine, Wayne State University, 110 E. Warren Ave., Detroit, MI, 48201, USA

    Olga Radkevich-Brown, Jennifer B. Jacob, Richard F. Jones, Amy M. Weise & Wei-Zen Wei

Authors
  1. Paula J. Whittington
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  2. Olga Radkevich-Brown
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  3. Jennifer B. Jacob
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  4. Richard F. Jones
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  5. Amy M. Weise
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  6. Wei-Zen Wei
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Corresponding author

Correspondence to Wei-Zen Wei.

Additional information

P. J. Whittington, O. Radkevich-Brown and J. B. Jacob have contributed equally to this work.

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Whittington, P.J., Radkevich-Brown, O., Jacob, J.B. et al. Her-2 DNA versus cell vaccine: immunogenicity and anti-tumor activity. Cancer Immunol Immunother 58, 759–767 (2009). https://doi.org/10.1007/s00262-008-0599-x

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  • DOI: https://doi.org/10.1007/s00262-008-0599-x

Keywords

  • Her-2
  • Neu
  • DNA vaccine
  • Cancer vaccine