title: HER2-based recombinant immunogen to target DCs through FcγRs for cancer immunotherapy.
abstract: Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364-391) and the Fc domain of a human IgG(1). In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8(+) T cells from breast cancer patients.
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Italy.
authors.forename: Ilaria Grazia
authors.initials: IG
authors.lastname: Zizzari
authors.forename: Filippo
authors.initials: F
authors.lastname: Veglia
authors.forename: Federica
authors.initials: F
authors.lastname: Taurino
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahimi
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
authors.forename: Francesca
authors.initials: F
authors.lastname: Belleudi
authors.forename: Federica
authors.initials: F
authors.lastname: Riccardo
authors.forename: Morena
authors.initials: M
authors.lastname: Antonilli
authors.forename: Chiara
authors.initials: C
authors.lastname: Napoletano
authors.forename: Filippo
authors.initials: F
authors.lastname: Bellati
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Benedetti-Panici
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Marianna
authors.initials: M
authors.lastname: Nuti
authors.forename: Aurelia
authors.initials: A
authors.lastname: Rughetti
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins