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Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys

Gene Therapy volume 15, pages 1351–1360 (2008)Cite this article

Abstract

Her-2/neu is a well-characterized tumor-associated antigen, the overexpression of which in human carcinomas correlates with a poor prognosis. Here, we evaluated Her-2/neu-specific humoral and cellular immune responses in immunized monkeys after immunization with nonreplicating adenovirus (AdHM) expressing the extracellular and transmembrane domain of human Her-2/neu (HM) and/or naked DNA vaccine (pHM-hGM-CSF) expressing human granulocyte-macrophage colony-stimulating factor together with HM. Priming of monkeys with AdHM generated Her-2/neu-specific long-lasting antibody production. Furthermore, these Her-2/neu-specific antibodies produced by AdHM immunization, some of which shared epitope specificity with Herceptin, were able to induce antibody-dependent cellular cytotoxicity against Her-2-expressing target cells. Cellular immune responses were elicited in all monkeys immunized with Her-2/neu-expressing vaccine; interferon-γ was secreted when these splenocytes were restimulated with Her-2/neu-expressing autologous cells, and immunization with AdHM induced Her-2/neu-specific lymphoproliferative responses. Further, immunization with pHM-hGM-CSF before AdHM immunization noticeably enhanced cytotoxic T-lymphocyte activity. In addition, we observed no abnormalities that would indicate that the genetic vaccines had toxic effects in the immunized monkeys. Thus, we can conclude that our genetic vaccines efficiently elicited Her-2/neu-specific humoral and cellular immune responses without causing severe adverse effects in nonhuman primates and that as such they warrant further clinical investigation.

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Acknowledgements

We thank Dr Norman L Letvin (Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA) for the generous gift of S594 cell line.

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Author notes

  1. H-J Ko, Y-J Kim and Y-S Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea

    H-J Ko, Y-J Kim, Y-S Kim & C-Y Kang

  2. ViroMed Co., Ltd, Bongcheon-dong, Seoul, Korea

    J-M Kim, S-H Ho, J-G Jeong, S-M Oh & J-A Chae

  3. Division of Non-Clinical Studies, Korea Institute of Toxicology, Daejeon, Korea

    C-Y Kim & P-S Lee

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Correspondence to C-Y Kang.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Ko, HJ., Kim, YJ., Kim, YS. et al. Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys. Gene Ther 15, 1351–1360 (2008). https://doi.org/10.1038/gt.2008.81

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