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 |
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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 |
Keywords
- Cancer vaccine
- Hematopoietic stem cells
- HER-2
- Human immune system mice
- IL-12
- Metastasis
ASJC Scopus subject areas
- Cancer Research
- Oncology