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DNA vaccination strategies for anti-tumour effective gene therapy protocols

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Abstract

After more than 15 years of experimentation, DNA vaccines have become a promising perspective for tumour diseases, and animal models are widely used to study the biological features of human cancer progression and to test the efficacy of vaccination protocols. In recent years, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has revealed a number of advantages: antigen-specific DNA vaccination stimulates both cellular and humoral immune responses; multiple or multi-gene vectors encoding several antigens/determinants and immune-modulatory molecules can be delivered as single administration; DNA vaccination does not induce autoimmune disease in normal animals; DNA vaccines based on plasmid vectors can be produced and tested rapidly and economically. However, DNA vaccines have shown low immunogenicity when tested in human clinical trials, and compared with traditional vaccines, they induce weak immune responses. Therefore, the improvement of vaccine efficacy has become a critical goal in the development of effective DNA vaccination protocols for anti-tumour therapy. Several strategies are taken into account for improving the DNA vaccination efficacy, such as antigen optimisation, use of adjuvants and delivery systems like electroporation, co-expression of cytokines and co-stimulatory molecules in the same vector, different vaccination protocols. In this review we discuss how the combination of these approaches may contribute to the development of more effective DNA vaccination protocols for the therapy of lymphoma in a mouse model.

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Acknowledgments

E. Signori thanks “Energy for Research”, sponsor group of the Laboratory of Molecular Pathology and Experimental Oncology at CNR-INMM.This work was partly supported by Bio-Ker Srl and by MiUR, FIRB-Idee Progettuali RBIP0695BB_001. E. Massi is recipient of a post-doctoral fellowship from University Campus Bio-Medico of Rome, Centre of Integrated Research. S. Iurescia and D. Fioretti have been supported by MiUR grant FIRB 2006––Idee Progettuali (RBIP0695BB) and by Bio-Ker S.r.l.

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Authors and Affiliations

  1. CNR-Institute of Neurobiology and Molecular Medicine, Via Fosso del Cavaliere100, 00133, Rome, Italy

    Emanuela Signori, Sandra Iurescia, Emanuela Massi, Daniela Fioretti, Pieranna Chiarella, Mariangela De Robertis & Monica Rinaldi

  2. Section of Molecular Medicine and Biotechnology, PRABB, Centre of Integrated Research, Università Campus Bio-Medico di Roma, Via A. del Portillo 21, 00128, Rome, Italy

    Emanuela Signori, Emanuela Massi, Pieranna Chiarella, Mariangela De Robertis & Vito Michele Fazio

  3. Bio-ker S.r.l., POLARIS, Località Piscinamanna, 09010, Pula, Cagliari, Italy

    Giancarlo Tonon

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  1. Emanuela Signori
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  2. Sandra Iurescia
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  9. Vito Michele Fazio
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Correspondence to Emanuela Signori or Vito Michele Fazio.

Additional information

S. Iurescia, E. Massi, D. Fioretti, P. Chiarella and M. De Robertis are joint second authors and have contributed equally to this paper.

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Signori, E., Iurescia, S., Massi, E. et al. DNA vaccination strategies for anti-tumour effective gene therapy protocols. Cancer Immunol Immunother 59, 1583–1591 (2010). https://doi.org/10.1007/s00262-010-0853-x

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