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Immune-Reconstituted Influenza Virosome Containing CD40L Gene Enhances the Immunological and Protective Activity of a Carcinoembryonic Antigen Anticancer Vaccine

Maria Grazia Cusi^1,*, Maria Teresa Del Vecchio, Chiara Terrosi^*, Gianni Gori Savellini^*, Giuseppa Di Genova^*, Marco La Placa, Francesca Fallarino^¶, Christian Moser^||, Concetta Cardone, Giorgio Giorgi, Guido Francini and Pierpaolo Correale

^* Virology Section, Department of Molecular Biology, Medical Oncology Section, Pathology Section, Department of Human Pathology and Oncology, and Giorgio Segre Department of Pharmacology, Siena University School of Medicine, Siena, Italy;^¶ Pharmacology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy; and^|| Berna Biotech, Berne, Switzerland

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.

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