Human responses against HER-2-positive cancer cells in human immune system-engrafted mice.
Br J Cancer
; 107(8): 1302-9, 2012 Oct 09.
Article
em En
| MEDLINE
| ID: mdl-22929887
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Glicoproteínas
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Antígenos CD
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Receptor ErbB-2
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Antígenos CD34
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Vacinas Anticâncer
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Neoplasias Pulmonares
Limite:
Animals
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Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália