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 language | English |
|---|---|
| Pages (from-to) | 1302-1309 |
| Number of pages | 8 |
| Journal | British Journal of Cancer |
| Volume | 107 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Oct 9 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Human responses against HER-2-positive cancer cells in human immune system-engrafted mice
AU - De Giovanni, C.
AU - Nicoletti, G.
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.
PY - 2012/10/9
Y1 - 2012/10/9
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.
AB - 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.
KW - Cancer vaccine
KW - Hematopoietic stem cells
KW - HER-2
KW - Human immune system mice
KW - IL-12
KW - Metastasis
UR - http://www.scopus.com/inward/record.url?scp=84867399067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867399067&partnerID=8YFLogxK
U2 - 10.1038/bjc.2012.394
DO - 10.1038/bjc.2012.394
M3 - Article
C2 - 22929887
AN - SCOPUS:84867399067
VL - 107
SP - 1302
EP - 1309
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 8
ER -