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Immuno-gene therapy of melanoma by tumor antigen epitope modified IFN-γ

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Abstract

Cytokine-based vaccines play a major part in tumor immuno-gene therapy. However, down-regulated antigen expression on tumor cells may diminish the immuno-potentiating aspects of cellular vaccines. In this study, we coexpressed a tumor antigen epitope with IFN-γ in the same gene by replacing the IFN-γ signal peptide with an antigen epitope-expressing signal peptide. We then investigated the effect of the antigen epitope-incorporated IFN-γ on the immunotherapy of murine melanoma B16 tumors. Results showed that TRP-2 epitope-expressing IFN-γ decreased B16 tumorigenicity and enhanced its immunogenicity after gene transfer. Protective immunity against wild type B16 tumors was induced by vaccination with IFN-γ transiently gene-modified tumor cells. These data suggest that cellular vaccines engineered to express an antigen epitope within an immunostimulatory cytokine could potentiate the immunization effect.

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Authors and Affiliations

  1. Gene Therapy Group, Department of Microbiology and Immunology, Arizona Health Sciences Center, University of Arizona, Tucson, 245049, AZ, 85724, USA

    Xianghui He, Tom C Tsang & David T Harris

  2. Cardiovascular Research Department, St. Elizabeth Medical Center, Tufts University, Boston, MA, 02135, USA

    Phoebe Luo

  3. Department of Microbiology and Immunology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03766, USA

    Tong Zhang

Authors
  1. Xianghui He
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  2. Phoebe Luo
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  3. Tom C Tsang
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  4. Tong Zhang
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  5. David T Harris
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Correspondence to David T Harris.

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He, X., Luo, P., Tsang, T.C. et al. Immuno-gene therapy of melanoma by tumor antigen epitope modified IFN-γ. Cancer Immunol Immunother 54, 741–749 (2005). https://doi.org/10.1007/s00262-004-0634-5

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  • DOI: https://doi.org/10.1007/s00262-004-0634-5

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