IMMUNOPHARMACOLOGICAL PREVENTION OF ORAL SQUAMOUS CELL CARCINOMA THROUGH DNA VACCINATION BY ELECTROPORATION: A PRECLINICAL STUDY. The Her-2/ receptor neu gene encodes a p185 tyrosine kinase growth factor receptor homologous to other members of the epidermal growth factor family. Overexpressed or mutated p185 transduces positive growth signals in a ligand-independent way, and is therefore involved in the initiation and progression of neoplastic transformation. An increased Her-2/neu gene copy number and/or excess cell membrane expression of p185 is a frequent event in oral squamous cell carcinoma, the most common type of oral neoplasm, and is correlated with poor survival. We therefore considered this receptor an appropriate target to assess whether DNA vaccination with plasmids coding a portion of the p185 elicits a protective immune response in prevention of the development of oral tumor induced in Syrian hamsters by inoculation of Her-2/neu positive tumor cells. Intramuscular vaccinations with a plasmid encoding the extracellular and transmembrane domains of the HER-2/neu p185, or of the empty plasmid as a control, were injected bilaterally in the tibialis anterior of rodents. Injections were followed by two electric pulses that create a series of holes in the membrane, helping DNA to enter the cells and inducing a more stable “in vivo” expression of the antigen. Antibody titre against p185 was checked. We then inoculated submucosally in the buccal pouch of Syrian hamsters 18x106 HCPC1 cells previously shown to be p185 positive (orthotopic model). Lesion evolution was monitored weekly. In our animal model we could appreciate an important difference between vaccinated and untreated animals. Our data suggest that DNA vaccination could be a new immunopharmacological approach to prevent the development of oral tumor, with interesting possible future clinical applications.
Immunopharmacological prevention of oral squamous cell carcinoma through DNA vaccination by electroporarion: a preclinical study
BERTA, Giovanni Nicolao
2005-01-01
Abstract
IMMUNOPHARMACOLOGICAL PREVENTION OF ORAL SQUAMOUS CELL CARCINOMA THROUGH DNA VACCINATION BY ELECTROPORATION: A PRECLINICAL STUDY. The Her-2/ receptor neu gene encodes a p185 tyrosine kinase growth factor receptor homologous to other members of the epidermal growth factor family. Overexpressed or mutated p185 transduces positive growth signals in a ligand-independent way, and is therefore involved in the initiation and progression of neoplastic transformation. An increased Her-2/neu gene copy number and/or excess cell membrane expression of p185 is a frequent event in oral squamous cell carcinoma, the most common type of oral neoplasm, and is correlated with poor survival. We therefore considered this receptor an appropriate target to assess whether DNA vaccination with plasmids coding a portion of the p185 elicits a protective immune response in prevention of the development of oral tumor induced in Syrian hamsters by inoculation of Her-2/neu positive tumor cells. Intramuscular vaccinations with a plasmid encoding the extracellular and transmembrane domains of the HER-2/neu p185, or of the empty plasmid as a control, were injected bilaterally in the tibialis anterior of rodents. Injections were followed by two electric pulses that create a series of holes in the membrane, helping DNA to enter the cells and inducing a more stable “in vivo” expression of the antigen. Antibody titre against p185 was checked. We then inoculated submucosally in the buccal pouch of Syrian hamsters 18x106 HCPC1 cells previously shown to be p185 positive (orthotopic model). Lesion evolution was monitored weekly. In our animal model we could appreciate an important difference between vaccinated and untreated animals. Our data suggest that DNA vaccination could be a new immunopharmacological approach to prevent the development of oral tumor, with interesting possible future clinical applications.
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