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

Berta GN, Mognetti B, Spadaro M, Trione E, Amici A, Forni G, Di Carlo F, Cavallo F - Br. J. Cancer (2005)

Bottom Line: This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) 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.These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Biological Sciences, Ospedale San Luigi Gonzaga, University of Turin, I-10043 Orbassano, Italy. giovanni.berta@unito.it

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(-1) 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]anthracene-induced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) 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.

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Specific antibodies against p185. (A) Anti p185-antibody titre in vaccinated and control animals. Mean antibody titres are indicated by full line (**P=0.0024). Antibody titre of EC-TM DNA-vax hamsters is correlated to vaccination outcome: black and empty triangles represent tumour-rejecting and tumor-bearing animals, respectively. Only two out of seven tumour-bearing hamsters displayed an antibody titre above 11.5 μg ml−1 (dotted line). (B) Extracts of healthy mucosa (lane 1), tumour tissue (lane 2) and HCPC I (lane 3) immunoprecipitated by Sc-284 and revealed with pooled sera from DNA-vax hamsters. The arrow indicates a molecular weight of 185 kDa.
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fig4: Specific antibodies against p185. (A) Anti p185-antibody titre in vaccinated and control animals. Mean antibody titres are indicated by full line (**P=0.0024). Antibody titre of EC-TM DNA-vax hamsters is correlated to vaccination outcome: black and empty triangles represent tumour-rejecting and tumor-bearing animals, respectively. Only two out of seven tumour-bearing hamsters displayed an antibody titre above 11.5 μg ml−1 (dotted line). (B) Extracts of healthy mucosa (lane 1), tumour tissue (lane 2) and HCPC I (lane 3) immunoprecipitated by Sc-284 and revealed with pooled sera from DNA-vax hamsters. The arrow indicates a molecular weight of 185 kDa.

Mentions: A significant anti-HER-2 antibody response was detected in sera collected the day before HCPC I challenge from the immunised hamsters. Most of the hamsters that rejected the challenge displayed the highest antibody titres (Figure 4A). These titres were much the same 5 weeks later.


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

Berta GN, Mognetti B, Spadaro M, Trione E, Amici A, Forni G, Di Carlo F, Cavallo F - Br. J. Cancer (2005)

Specific antibodies against p185. (A) Anti p185-antibody titre in vaccinated and control animals. Mean antibody titres are indicated by full line (**P=0.0024). Antibody titre of EC-TM DNA-vax hamsters is correlated to vaccination outcome: black and empty triangles represent tumour-rejecting and tumor-bearing animals, respectively. Only two out of seven tumour-bearing hamsters displayed an antibody titre above 11.5 μg ml−1 (dotted line). (B) Extracts of healthy mucosa (lane 1), tumour tissue (lane 2) and HCPC I (lane 3) immunoprecipitated by Sc-284 and revealed with pooled sera from DNA-vax hamsters. The arrow indicates a molecular weight of 185 kDa.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2361512&req=5

fig4: Specific antibodies against p185. (A) Anti p185-antibody titre in vaccinated and control animals. Mean antibody titres are indicated by full line (**P=0.0024). Antibody titre of EC-TM DNA-vax hamsters is correlated to vaccination outcome: black and empty triangles represent tumour-rejecting and tumor-bearing animals, respectively. Only two out of seven tumour-bearing hamsters displayed an antibody titre above 11.5 μg ml−1 (dotted line). (B) Extracts of healthy mucosa (lane 1), tumour tissue (lane 2) and HCPC I (lane 3) immunoprecipitated by Sc-284 and revealed with pooled sera from DNA-vax hamsters. The arrow indicates a molecular weight of 185 kDa.
Mentions: A significant anti-HER-2 antibody response was detected in sera collected the day before HCPC I challenge from the immunised hamsters. Most of the hamsters that rejected the challenge displayed the highest antibody titres (Figure 4A). These titres were much the same 5 weeks later.

Bottom Line: This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) 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.These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Biological Sciences, Ospedale San Luigi Gonzaga, University of Turin, I-10043 Orbassano, Italy. giovanni.berta@unito.it

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(-1) 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]anthracene-induced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) 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.

Show MeSH
Related in: MedlinePlus