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Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2

Abstract

RNA-based genetic immunization represents an alternative novel strategy for antigen-specific cancer vaccines. In the present paper we investigate the use of synthetic messenger RNA in an experimental melanoma model. We show that gene gun-based immunization using synthetic RNA mediates gene expression in the epidermis and effectively induces antigen-specific cellular and humoral immunity in mice in vivo. Importantly, bombardment of the skin with RNA coding for the melanocytic self-antigen TRP2 linked to the immunogenic protein EGFP was associated with protection against experimentally induced B16 melanoma lung metastases and vitiligo-like fur depigmentation. Our results provide a scientific basis for clinical trials using synthetic mRNA encoding melanocytic antigens linked to immunogenic helper proteins for vaccination of patients with melanoma.

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Abbreviations

EGFP:

Enhanced green fluorescent protein

mTRP2:

Murine tyrosinase-related protein 2

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Acknowledgements

We thank Stefanie Büchs and Petra Speuser for excellent technical assistance. This work was supported by the ’‘Deutsche Forschungsgemeinschaft” (For 367/2 to TT and SFB432/A1 to TW) and by the “Deutsche Krebshilfe” (70–2427-Hul to TW and 10–1870-Tü2 to TT).

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Correspondence to Thomas Tüting.

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Julia Steitz and Cedrik M. Britten contributed equally to this work.

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Steitz, J., Britten, C.M., Wölfel, T. et al. Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2. Cancer Immunol Immunother 55, 246–253 (2006). https://doi.org/10.1007/s00262-005-0042-5

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Keywords

  • RNA
  • Melanoma
  • Vaccine
  • TRP2