Human responses against HER-2-positive cancer cells in human immune system-engrafted mice

C. De Giovanni, G. Nicoletti, L. Landuzzi, F. Romani, S. Croci, A. Palladini, A. Murgo, A. Antognoli, M. L. Ianzano, V. Stivani, V. Grosso, M. Iezzi, L. Stramucci, E. Barbieri, R. M. Lemoli, P. Nanni, P. L. Lollini

Research output: Contribution to journalArticle

Abstract

Background: Human immune system (HIS)-engrafted mice are new tools to investigate human immune responses. Here, we used HIS mice to study human immune responses against human HER-2-positive cancer cells and their ability to control tumour growth and metastasis. Methods: BALB/c Rag2-/-, Il2rg-/- mice were engrafted with CD34+ or CD133 + human cord blood hematopoietic stem cells (HSC) and vaccinated with human HER-2-positive cancer cells SK-OV-3 combined to human IL-12. Results: Both CD34+ or CD133+ human HSC gave long-term engraftment and differentiation, both in peripheral blood and in lymphoid organs, and production of human antibodies. Vaccinated mice produced specific anti-HER-2 human IgG. An s.c. SK-OV-3 challenge was significantly inhibited (but not abolished) in both vaccinated and non-vaccinated HIS mice. Tumours were heavily infiltrated with human and murine cells, mice showed NK cells and production of human interferon-γ, that could contribute to tumour growth inhibition. Vaccinated HIS mice showed significantly inhibited lung metastases when compared with non-vaccinated HIS mice and to non-HIS mice, along with higher levels of tumour-infiltrating human dendritic cells. Conclusion: Anti-HER-2 responses were elicited through an adjuvanted allogeneic cancer cell vaccine in HIS mice. Human immune responses elicited in HIS mice effectively inhibited lung metastases.

Original languageEnglish
Pages (from-to)1302-1309
Number of pages8
JournalBritish Journal of Cancer
Volume107
Issue number8
DOIs
Publication statusPublished - Oct 9 2012

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Immune System
Neoplasms
Neoplasm Metastasis
Hematopoietic Stem Cells
Lung
Cancer Vaccines
Interleukin-12
Growth
Fetal Blood
Natural Killer Cells
Dendritic Cells
Interferons
Antibody Formation

Keywords

  • Cancer vaccine
  • Hematopoietic stem cells
  • HER-2
  • Human immune system mice
  • IL-12
  • Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human responses against HER-2-positive cancer cells in human immune system-engrafted mice. / De Giovanni, C.; Nicoletti, G.; Landuzzi, L.; Romani, F.; Croci, S.; Palladini, A.; Murgo, A.; Antognoli, A.; Ianzano, M. L.; Stivani, V.; Grosso, V.; Iezzi, M.; Stramucci, L.; Barbieri, E.; Lemoli, R. M.; Nanni, P.; Lollini, P. L.

In: British Journal of Cancer, Vol. 107, No. 8, 09.10.2012, p. 1302-1309.

Research output: Contribution to journalArticle

De Giovanni, C, Nicoletti, G, Landuzzi, L, Romani, F, Croci, S, Palladini, A, Murgo, A, Antognoli, A, Ianzano, ML, Stivani, V, Grosso, V, Iezzi, M, Stramucci, L, Barbieri, E, Lemoli, RM, Nanni, P & Lollini, PL 2012, 'Human responses against HER-2-positive cancer cells in human immune system-engrafted mice', British Journal of Cancer, vol. 107, no. 8, pp. 1302-1309. https://doi.org/10.1038/bjc.2012.394
De Giovanni, C. ; Nicoletti, G. ; Landuzzi, L. ; Romani, F. ; Croci, S. ; Palladini, A. ; Murgo, A. ; Antognoli, A. ; Ianzano, M. L. ; Stivani, V. ; Grosso, V. ; Iezzi, M. ; Stramucci, L. ; Barbieri, E. ; Lemoli, R. M. ; Nanni, P. ; Lollini, P. L. / Human responses against HER-2-positive cancer cells in human immune system-engrafted mice. In: British Journal of Cancer. 2012 ; Vol. 107, No. 8. pp. 1302-1309.
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AU - Landuzzi, L.

AU - Romani, F.

AU - Croci, S.

AU - Palladini, A.

AU - Murgo, A.

AU - Antognoli, A.

AU - Ianzano, M. L.

AU - Stivani, V.

AU - Grosso, V.

AU - Iezzi, M.

AU - Stramucci, L.

AU - Barbieri, E.

AU - Lemoli, R. M.

AU - Nanni, P.

AU - Lollini, P. L.

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N2 - Background: Human immune system (HIS)-engrafted mice are new tools to investigate human immune responses. Here, we used HIS mice to study human immune responses against human HER-2-positive cancer cells and their ability to control tumour growth and metastasis. Methods: BALB/c Rag2-/-, Il2rg-/- mice were engrafted with CD34+ or CD133 + human cord blood hematopoietic stem cells (HSC) and vaccinated with human HER-2-positive cancer cells SK-OV-3 combined to human IL-12. Results: Both CD34+ or CD133+ human HSC gave long-term engraftment and differentiation, both in peripheral blood and in lymphoid organs, and production of human antibodies. Vaccinated mice produced specific anti-HER-2 human IgG. An s.c. SK-OV-3 challenge was significantly inhibited (but not abolished) in both vaccinated and non-vaccinated HIS mice. Tumours were heavily infiltrated with human and murine cells, mice showed NK cells and production of human interferon-γ, that could contribute to tumour growth inhibition. Vaccinated HIS mice showed significantly inhibited lung metastases when compared with non-vaccinated HIS mice and to non-HIS mice, along with higher levels of tumour-infiltrating human dendritic cells. Conclusion: Anti-HER-2 responses were elicited through an adjuvanted allogeneic cancer cell vaccine in HIS mice. Human immune responses elicited in HIS mice effectively inhibited lung metastases.

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