Abstract
Introduction: The availability of mice transgenic for the human HER2 gene (huHER2) and prone to the development of HER2-driven mammary carcinogenesis (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive strategies targeting the human HER2 molecule in a tolerant host.Methods: FVB-huHER2 mice were vaccinated with either IL-12-adjuvanted human HER2-positive cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and number of mammary tumors were recorded to evaluate vaccine potency. Mice sera were collected and passively transferred to xenograft-bearing mice to assess their antitumor efficacy.Results: Both cell and DNA vaccines significantly delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of 45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about 90 weeks of age. The number of mammary tumors per mouse was also significantly reduced in vaccinated mice. Vaccines broke the immunological tolerance to the huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine mainly induced a high and sustained level of anti-huHER2 antibodies, the cell vaccine also elicited interferon (IFN)-γ production. Sera of DNA-vaccinated mice transferred to xenograft-carrying mice significantly inhibited the growth of human HER2-positive cancer cells.Conclusions: Anti-huHER2 antibodies elicited in the tolerant host exert antitumor activity.
| Original language | English |
|---|---|
| Article number | R10 |
| Journal | Breast Cancer Research |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 23 2014 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
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Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2. / De Giovanni, Carla; Nicoletti, Giordano; Quaglino, Elena; Landuzzi, Lorena; Palladini, Arianna; Ianzano, Marianna Lucia; Dall'Ora, Massimiliano; Grosso, Valentina; Ranieri, Dario; Laranga, Roberta; Croci, Stefania; Amici, Augusto; Penichet, Manuel L.; Iezzi, Manuela; Cavallo, Federica; Nanni, Patrizia; Lollini, Pier Luigi.
In: Breast Cancer Research, Vol. 16, No. 1, R10, 23.01.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2
AU - De Giovanni, Carla
AU - Nicoletti, Giordano
AU - Quaglino, Elena
AU - Landuzzi, Lorena
AU - Palladini, Arianna
AU - Ianzano, Marianna Lucia
AU - Dall'Ora, Massimiliano
AU - Grosso, Valentina
AU - Ranieri, Dario
AU - Laranga, Roberta
AU - Croci, Stefania
AU - Amici, Augusto
AU - Penichet, Manuel L.
AU - Iezzi, Manuela
AU - Cavallo, Federica
AU - Nanni, Patrizia
AU - Lollini, Pier Luigi
PY - 2014/1/23
Y1 - 2014/1/23
N2 - Introduction: The availability of mice transgenic for the human HER2 gene (huHER2) and prone to the development of HER2-driven mammary carcinogenesis (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive strategies targeting the human HER2 molecule in a tolerant host.Methods: FVB-huHER2 mice were vaccinated with either IL-12-adjuvanted human HER2-positive cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and number of mammary tumors were recorded to evaluate vaccine potency. Mice sera were collected and passively transferred to xenograft-bearing mice to assess their antitumor efficacy.Results: Both cell and DNA vaccines significantly delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of 45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about 90 weeks of age. The number of mammary tumors per mouse was also significantly reduced in vaccinated mice. Vaccines broke the immunological tolerance to the huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine mainly induced a high and sustained level of anti-huHER2 antibodies, the cell vaccine also elicited interferon (IFN)-γ production. Sera of DNA-vaccinated mice transferred to xenograft-carrying mice significantly inhibited the growth of human HER2-positive cancer cells.Conclusions: Anti-huHER2 antibodies elicited in the tolerant host exert antitumor activity.
AB - Introduction: The availability of mice transgenic for the human HER2 gene (huHER2) and prone to the development of HER2-driven mammary carcinogenesis (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive strategies targeting the human HER2 molecule in a tolerant host.Methods: FVB-huHER2 mice were vaccinated with either IL-12-adjuvanted human HER2-positive cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and number of mammary tumors were recorded to evaluate vaccine potency. Mice sera were collected and passively transferred to xenograft-bearing mice to assess their antitumor efficacy.Results: Both cell and DNA vaccines significantly delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of 45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about 90 weeks of age. The number of mammary tumors per mouse was also significantly reduced in vaccinated mice. Vaccines broke the immunological tolerance to the huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine mainly induced a high and sustained level of anti-huHER2 antibodies, the cell vaccine also elicited interferon (IFN)-γ production. Sera of DNA-vaccinated mice transferred to xenograft-carrying mice significantly inhibited the growth of human HER2-positive cancer cells.Conclusions: Anti-huHER2 antibodies elicited in the tolerant host exert antitumor activity.
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UR - http://www.scopus.com/inward/citedby.url?scp=84892715075&partnerID=8YFLogxK
U2 - 10.1186/bcr3602
DO - 10.1186/bcr3602
M3 - Article
C2 - 24451168
AN - SCOPUS:84892715075
VL - 16
JO - Breast Cancer Research
JF - Breast Cancer Research
SN - 1465-5411
IS - 1
M1 - R10
ER -