title: Human responses against HER-2-positive cancer cells in human immune system-engrafted mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental Pathology, Cancer Research Section, Alma Mater Studiorum Università di Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: De Giovanni
authors.forename: G
authors.initials: G
authors.lastname: Nicoletti
authors.forename: L
authors.initials: L
authors.lastname: Landuzzi
authors.forename: F
authors.initials: F
authors.lastname: Romani
authors.forename: S
authors.initials: S
authors.lastname: Croci
authors.forename: A
authors.initials: A
authors.lastname: Palladini
authors.forename: A
authors.initials: A
authors.lastname: Murgo
authors.forename: A
authors.initials: A
authors.lastname: Antognoli
authors.forename: M L
authors.initials: ML
authors.lastname: Ianzano
authors.forename: V
authors.initials: V
authors.lastname: Stivani
authors.forename: V
authors.initials: V
authors.lastname: Grosso
authors.forename: M
authors.initials: M
authors.lastname: Iezzi
authors.forename: L
authors.initials: L
authors.lastname: Stramucci
authors.forename: E
authors.initials: E
authors.lastname: Barbieri
authors.forename: R M
authors.initials: RM
authors.lastname: Lemoli
authors.forename: P
authors.initials: P
authors.lastname: Nanni
authors.forename: P-L
authors.initials: PL
authors.lastname: Lollini
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D019496:Cancer Vaccines; D006023:Glycoproteins; D007132:Immunoglobulin Isotypes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C000606023:PROM1 protein, human; C000606024:Prom1 protein, mouse; C508053:ERBB2 protein, human