title: Immune-reconstituted influenza virosome containing CD40L gene enhances the immunological and protective activity of a carcinoembryonic antigen anticancer vaccine.
abstract: The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation. This process can be exploited to significantly improve the efficacy of cancer vaccines and the outcome of a possible cancer vaccine-induced, Ag-specific CTL response. Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV). Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype. In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
authors.affiliation: Virology Section, Department of Molecular Biology, Siena University School of Medicine, Italy. cusi@unisi.it
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Del Vecchio
authors.forename: Chiara
authors.initials: C
authors.lastname: Terrosi
authors.forename: Gianni Gori
authors.initials: GG
authors.lastname: Savellini
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Di Genova
authors.forename: Marco
authors.initials: M
authors.lastname: La Placa
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Christian
authors.initials: C
authors.lastname: Moser
authors.forename: Concetta
authors.initials: C
authors.lastname: Cardone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giorgi
authors.forename: Guido
authors.initials: G
authors.lastname: Francini
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000235:genetics* / Q000627:therapeutic use; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D007252:Influenza Vaccines / Q000138:chemical synthesis / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D017778:Vaccines, Combined / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D022721:Vaccines, Virosome / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; C497965:Cd86 protein, mouse; D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines; D008562:Membrane Glycoproteins; D017778:Vaccines, Combined; D022721:Vaccines, Virosome; D023201:CD40 Ligand