Anti-HER-2 DNA vaccine protects Syrian hamsters against squamous cell carcinomas

Abstract

This paper illustrates the efficacy of DNA vaccination through electroporation in the prevention of oral transplantable carcinoma in Syrian hamsters. At 21 and 7 days before tumour challenge, 19 hamsters were vaccinated with plasmids coding for the extracellular and transmembrane domains of rat HER-2 receptor (EC-TM plasmids), whereas 19 control hamsters were injected intramuscularly with the empty plasmid. Immediately following plasmid injection, hamsters of both groups received two square-wave 25 ms, 375 V cm À1 electric pulses via two electrodes placed on the skin of the injection area. At day 0, all hamsters were challenged in the submucosa of the right cheek pouch with HER-2-positive HCPC I cells established in vitro from an 7,12-dimethylbenz[a]anthraceneinduced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, Po0.0027) vaccinated hamsters. In addition, the vaccinated hamsters displayed both a stronger proliferative and cytotoxic response than the controls and a significant anti-HER-2 antibody response. Most of the hamsters that rejected the challenge displayed the highest antibody titres. These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.

A DNA Vaccine against ERBB2 Impairs Chemical Carcinogenesis in Random-Bred Hamsters

“…The collaboration of antibody-and cellmediated cytotoxic responses in protection against ERBB2 þ tumors has been clearly documented (27). We have previously shown that electroporation of the EC-TM plasmid in hamsters elicits a protective anti-ERBB2 antibody-and cell-mediated cytotoxic response against ERBB2 þ transplantable tumors (21). In the present study, a similar cytotoxic response was also elicited in the few ERBB2 vaccinated hamsters tested (data not shown).…”

“…However, it is a self-tolerated molecule and triggering a response against it has to circumvent central and peripheral tolerance (4,15). Data in mice (24) and hamsters (21) have shown that EC-TM plasmid electroporation is an effective way to break tolerance. However, the antibody response thus induced is short lived and frequent electroporations are required for a sustained control of carcinogenesis (24).…”

“…To determine whether induction of the immune response against ERBB2 impairs a chemically driven carcinogenesis, 40 hamsters were electroporated every 3 weeks with EC-TM plasmids (21,24). Thirty control hamsters Figure 3.…”

“…The EC-TM plasmid and the empty control plasmid (pcDNA3) were produced and used as we have previously described in detail (21). Briefly, anesthetized hamsters were electroporated by injecting 50 mg of plasmids in 40 mL of 0.9% NaCl supplemented with 6 mg/mL polyglutamate into both tibial muscles.…”

Electroporation-Mediated Gene Delivery

“…For example, in one study in hamsters, the HER2 receptor was expressed in skin via electroporation and subsequently, the animals were challenged with HER2 positive carcinogen-induced oral carcinoma cells. Thirty-seven percent of animals that received the HER2 gene developed neoplasia compared to 74% of control animals (Berta et al, 2005). …”