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A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma

Cancer Gene Therapy volume 10, pages 678–688 (2003)Cite this article

Abstract

A mouse glioblastoma cell line, termed GL261, was shown to express high levels of proteins involved in melanin biosynthesis such as the tyrosinase-related protein-2 (TRP-2), which is commonly overexpressed in melanoma cells. Mice injected with GL261 cells developed a CD8+ T-cell response to TRP-2 and a DNA vaccine expressing human (h)TRP-2 induced CD8+ T cells that recognized TRP-2 expressed by GL261 cells indicating that this melanoma-associated antigen may be suited for active immunotherapy of glioblastoma. Mice vaccinated with a DNA vaccine expressing TRP-2 were partially protected against subcutaneous, intravenous, or intracerebral challenge with the glioblastoma cells. Vaccine-induced protection against intracerebral challenge required both CD4+ and CD8+ T cells. Vaccine efficacy was enhanced upon addition of IL-12 as a genetic adjuvant. These results indicate that this well-defined melanoma-associated antigen can induce an adaptive immune response, which limits the intracerebral progression of a glioblastoma.

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Acknowledgements

We would like to thank Ms W Giles-Davis for technical assistance and Ms Cole for preparation of the manuscript. This work was supported by a grant from the Katie's Kids Brain Tumor Foundation.

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  1. Magdalena Blaszczyk-Thurin

    Present address: Cancer Diagnosis Program, DCTD, NCI, NIH, EPN 6035A, 6130 Executive Blvd., Rockville, MD, 20892, USA

Authors and Affiliations

  1. The Wistar Institute, 3601 Spruce Street, Philadelphia, 19104, Pennsylvania, USA

    InSug O, Magdalena Blaszczyk-Thurin, Chunpang T Shen & Hildegund CJ Ertl

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Correspondence to Hildegund CJ Ertl.

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O, I., Blaszczyk-Thurin, M., Shen, C. et al. A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma. Cancer Gene Ther 10, 678–688 (2003). https://doi.org/10.1038/sj.cgt.7700620

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