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Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu

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Abstract

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund’s adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.

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Acknowledgements

We would like to thank Dr. Joseph D. Rosenblatt (Department of Medicine, University of Miami School of Medicine, Miami, FL) for providing the EL4-Her-2 cells. We also like to thank Mary B. Palascak and Peter Ciraolo for help in flow cytometry. This work was supported by the NIH Grant RO1 CA91878.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Cincinnati, The Vontz Center for Molecular Studies, 3125 Eden Avenue, Cincinnati, OH, 45267, USA

    Kartik Mohanty, Asim Saha, Smarajit Pal, Palash Mallick, Sunil K. Chatterjee & Malaya Bhattacharya-Chatterjee

  2. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Kenneth A. Foon

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  1. Kartik Mohanty
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  2. Asim Saha
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  7. Malaya Bhattacharya-Chatterjee
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Correspondence to Malaya Bhattacharya-Chatterjee.

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Asim Saha and Smarajit Pal contributed equally to this work.

This work was presented as abstract in the San Antonio Breast Cancer Symposium, 2005. Breast Cancer Research and Treatment 94, supplement 1:4093.

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Mohanty, K., Saha, A., Pal, S. et al. Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu. Breast Cancer Res Treat 104, 1–11 (2007). https://doi.org/10.1007/s10549-006-9391-9

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  • DOI: https://doi.org/10.1007/s10549-006-9391-9

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