title: HER-2/neu tolerant and non-tolerant mice for fine assessment of antimetastatic potency of dendritic cell-tumor cell hybrid vaccines.
abstract: Main obstacles to cancer vaccine efficacy are pre-existing antigenic load and immunoescape mechanisms, including tolerance against self tumor-associated antigens. Here we explored the role of tolerance in an antimetastatic vaccine approach based on dendritic cell-tumor cell (DC-TC) hybrids, thanks to the comparison between BALB-neuT mice, transgenic for and tolerant to rat HER-2/neu, with their non-tolerant strain of origin BALB/c. Allogeneic DC-TC hybrid vaccine displayed a high antimetastatic activity in non-tolerant mice, but was far less effective in tolerant mice, even with intensified vaccine schedule. Tolerant BALB-neuT mice revealed a reduced ability to mount polarized Th1 responses. A further attempt to increase the antimetastatic activity by using LPS-matured DC hybrids failed. Allogeneic LPS-matured DC-TC hybrids induced high IFN-γ levels, but concomitantly also the highest production of IL-4 and IL-10 suggesting activation of mechanisms sustaining regulatory cells able to blunt vaccine efficacy. Our data in tolerant versus non-tolerant hosts suggest that clinical translation of effective DC-based strategies could benefit from more extensive investigations in tolerant transgenic models.
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Landuzzi
authors.forename: Agnese
authors.initials: A
authors.lastname: Antognoli
authors.forename: Giordano
authors.initials: G
authors.lastname: Nicoletti
authors.forename: Stefania
authors.initials: S
authors.lastname: Croci
authors.forename: Arianna
authors.initials: A
authors.lastname: Palladini
authors.forename: Marianna Lucia
authors.initials: ML
authors.lastname: Ianzano
authors.forename: Annalisa
authors.initials: A
authors.lastname: Murgo
authors.forename: Valeria
authors.initials: V
authors.lastname: Stivani
authors.forename: Valentina
authors.initials: V
authors.lastname: Grosso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nanni
authors.forename: Carla
authors.initials: C
authors.lastname: De Giovanni
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Lollini
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006822:Hybrid Cells / Q000276:immunology*; D007108:Immune Tolerance; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; C483804:Erbb2 protein, rat