Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2

Carla De Giovanni, Giordano Nicoletti, Elena Quaglino, Lorena Landuzzi, Arianna Palladini, Marianna Lucia Ianzano, Massimiliano Dall'Ora, Valentina Grosso, Dario Ranieri, Roberta Laranga, Stefania Croci, Augusto Amici, Manuel L. Penichet, Manuela Iezzi, Federica Cavallo, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticle

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 languageEnglish
Article numberR10
JournalBreast Cancer Research
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 23 2014

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Transgenic Mice
erbB-2 Genes
Vaccines
Breast Neoplasms
DNA Vaccines
Heterografts
Neoplasms
Vaccine Potency
Cancer Vaccines
Antibodies
DNA
Interleukin-12
Serum
Transgenes
Interferons
Carcinogenesis
Breast
Cytokines
Growth

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 journalArticle

De Giovanni, C, Nicoletti, G, Quaglino, E, Landuzzi, L, Palladini, A, Ianzano, ML, Dall'Ora, M, Grosso, V, Ranieri, D, Laranga, R, Croci, S, Amici, A, Penichet, ML, Iezzi, M, Cavallo, F, Nanni, P & Lollini, PL 2014, 'Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2', Breast Cancer Research, vol. 16, no. 1, R10. https://doi.org/10.1186/bcr3602
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. / Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2. In: Breast Cancer Research. 2014 ; Vol. 16, No. 1.
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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.",
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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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