HER-2 is a tyrosine kinase receptor involved in the progression of many epithelial tumors, including the oral squamous cell carcinoma (OSCC). Despite pharmacological enhancements, surgery is still the choice treatment, but often resulting in chronic pain, speech/swallowing impediments, and irreparable/disfiguring impairments. Here we evaluated if anti-HER-2 DNA vaccination may prevents the OSCC occurrence in HER-2+-OSCC-engrafted Syrian hamsters. Three and one weeks before tumor challenge hamsters were vaccinated with plasmids coding for extracellular and transmembrane domains of rat HER-2 receptor (EC-TM), or with the empty pCDNA3 vector. Then, hamster DMBAinduced-OSCC HER-2+ cells (HCPC-I) were submucosally injected in the right cheek pouch. It gave rise to HER-2+ lesions in both groups. Despite severity of cancer lesions was similar, occurrence was proven in the 73.4% of controls and in the 36.8% of EC-TM vaccinated hamsters. Lesions were characterized by solid nests and cords composed of large roundish or, more commonly, elongated neoplastic cells, with occasional atypias, hyperchromatic nucleus and numerous mitoses, extensively infiltrating the wall of the pouch mucosa and underlying striated muscle fibers. Keratin pearls and multinucleated cells were occasionally observed, while foci of necrosis were present in most cases. EC-TM vaccinated hamsters displayed both stronger proliferative and cytotoxic response than the controls, and significant anti-HER-2 antibody reaction. Furthermore, most of the hamsters that rejected the challenge are characterized by high antibody titers. These findings suggest that the immune system triggering by DNA vaccination may have a translational perspective in the prevention of HER-2+ human oral cancer.
Anti-HER-2 DNA vaccine elicits protection against squamous cell carcinomas engraftment
SPRIO, ANDREA ELIO;SPADARO, Michela;SALAMONE, PAOLINA;DI SCIPIO, FEDERICA;CAVALLO, Federica;BERTA, Giovanni Nicolao
2011-01-01
Abstract
HER-2 is a tyrosine kinase receptor involved in the progression of many epithelial tumors, including the oral squamous cell carcinoma (OSCC). Despite pharmacological enhancements, surgery is still the choice treatment, but often resulting in chronic pain, speech/swallowing impediments, and irreparable/disfiguring impairments. Here we evaluated if anti-HER-2 DNA vaccination may prevents the OSCC occurrence in HER-2+-OSCC-engrafted Syrian hamsters. Three and one weeks before tumor challenge hamsters were vaccinated with plasmids coding for extracellular and transmembrane domains of rat HER-2 receptor (EC-TM), or with the empty pCDNA3 vector. Then, hamster DMBAinduced-OSCC HER-2+ cells (HCPC-I) were submucosally injected in the right cheek pouch. It gave rise to HER-2+ lesions in both groups. Despite severity of cancer lesions was similar, occurrence was proven in the 73.4% of controls and in the 36.8% of EC-TM vaccinated hamsters. Lesions were characterized by solid nests and cords composed of large roundish or, more commonly, elongated neoplastic cells, with occasional atypias, hyperchromatic nucleus and numerous mitoses, extensively infiltrating the wall of the pouch mucosa and underlying striated muscle fibers. Keratin pearls and multinucleated cells were occasionally observed, while foci of necrosis were present in most cases. EC-TM vaccinated hamsters displayed both stronger proliferative and cytotoxic response than the controls, and significant anti-HER-2 antibody reaction. Furthermore, most of the hamsters that rejected the challenge are characterized by high antibody titers. These findings suggest that the immune system triggering by DNA vaccination may have a translational perspective in the prevention of HER-2+ human oral cancer.
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