Immune-reconstituted influenza virosome containing CD40L gene enhances the immunological and protective activity of a carcinoembryonic antigen anticancer vaccine.
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.
Cusi
Maria Grazia
MG
Virology Section, Department of Molecular Biology, Siena University School of Medicine, Italy. cusi@unisi.it
Del Vecchio
Maria Teresa
MT
Terrosi
Chiara
C
Savellini
Gianni Gori
GG
Di Genova
Giuseppa
G
La Placa
Marco
M
Fallarino
Francesca
F
Moser
Christian
C
Cardone
Concetta
C
Giorgi
Giorgio
G
Francini
Guido
G
Correale
Pierpaolo
P
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
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