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Long-term immunity elicited by antibody–cytokine fusion proteins protects against sequential challenge with murine mammary and colon malignancies

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Abstract

We have previously reported that the antibody fusion proteins anti-HER2/neu IgG3 fused to IL-12 [(IL-12)-IgG3] or GM-CSF [IgG3-(GM-CSF)] independently or in combination are effective anti-tumor agents against D2F2/E2 murine mammary cancer cells expressing human HER2/neu in the peritoneum. Importantly, the long-term survivors were immune to the subcutaneous challenge with D2F2/E2 and the parental D2F2 not expressing HER2/neu. We now show that these long-term survivors also exhibit significant protection against subsequent subcutaneous challenge with the murine colon carcinoma CT26-HER2/neu, and later against subcutaneous challenge with the parental CT26. These results suggest that the long-term systemic protection against mammary cancer elicited by treatment with antibody–cytokine fusion proteins can be extended to prevent the growth of a tumor from different origin expressing HER2/neu, and that this protection is not limited to this antigen alone, since it also prevented the growth of the parental tumor cells.

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Acknowledgments

This work was supported in part by grants CA86915 and CA107023 from NCI and NIH, research supplement CMBB-NIH CA107023-02S1, MARC-NIH grant# GM08563-12, and the 2002 AACR-California Department of Health Services Career Development Award in Gender-related Cancer Research. CT26 cell line was a generous gift of Dr. Young Chul Sung, Pohang University of Science and Technology, South Korea. D2F2 and D2F2/E2 cell lines were kindly provided by Dr. Wei-Zen Wei, Wayne State University, Detroit, MI, USA.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Box 951782, Los Angeles, CA, 90095-1782, USA

    Gustavo Helguera, José A. Rodríguez, Tracy R. Daniels & Manuel L. Penichet

  2. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Manuel L. Penichet

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  1. Gustavo Helguera
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  4. Manuel L. Penichet
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Correspondence to Manuel L. Penichet.

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Helguera, G., Rodríguez, J.A., Daniels, T.R. et al. Long-term immunity elicited by antibody–cytokine fusion proteins protects against sequential challenge with murine mammary and colon malignancies. Cancer Immunol Immunother 56, 1507–1512 (2007). https://doi.org/10.1007/s00262-007-0297-0

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