chimeric dna vaccines against erbb2+ carcinomas: from mice to humans

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ID: 141935
2011
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Ranked #132 of 132 articles by views in The Journal of investigative dermatology

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Abstract
DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2+ carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.
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macagno2011cancerschimeric Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Marco Macagno;Elena Quaglino;Federica Riccardo;Augusto Amici;Elisabetta Ercole;Rodica Cojoca;Silvio Bandini;Federica Cavallo
Journal The Journal of investigative dermatology
Year 2011
DOI
10.3390/cancers3033225
URL
http://www.mdpi.com/2072-6694/3/3/3225/
Keywords
Oncology including cancer and carcinogens tumors

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