title: Superior Immunologic and Therapeutic Efficacy of a Xenogeneic Genetic Cancer Vaccine Targeting Carcinoembryonic Human Antigen.
abstract: We have generated a xenogeneic vaccine against human carcinoembryonic antigen (hCEACAM-5 or commonly hCEA) using as immunogen rhesus CEA (rhCEA). RhCEA cDNA was codon-usage optimized (rhCEAopt) and delivered by sequential DNA electro-gene-transfer (DNA-EGT) and adenoviral (Ad) vector. RhCEAopt was capable to break tolerance to CEA in hCEA transgenic mice and immune responses were detected against epitopes distributed over the entire length of the protein. Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in addition to self-reactive CD8+ T-cells, the development of high-titer antibodies against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor cells. The superior activity of rhCEAopt compared with hCEAopt was confirmed in hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against specific human HLA A*0201 hCEA epitopes were detected. Our data show that xenogeneic gene-based vaccination with rhCEA is a viable approach to break tolerance against CEA, thus suggesting further development in the clinical setting.
authors: 1 Takis srl, 00128 Rome, Italy .
authors: Luigi
authors: L
authors: Aurisicchio
authors: 1 Takis srl, 00128 Rome, Italy .
authors: Giuseppe
authors: G
authors: Roscilli
authors: 1 Takis srl, 00128 Rome, Italy .
authors: Emanuele
authors: E
authors: Marra
authors: 1 Takis srl, 00128 Rome, Italy .|2 Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia ," Catanzaro, Italy .
authors: Laura
authors: L
authors: Luberto
authors: 3 Department of Clinical and Molecular Medicine, University of Rome "La Sapienza ," Rome, Italy .|4 Laboratory of Research and Diagnostics, Department of Surgery "P. Valdoni," University of Rome "La Sapienza ," Rome, Italy .
authors: Rita
authors: R
authors: Mancini
authors: 5 Johnson & Johnson Innovation Center , Cambridge, MA.
authors: Nicola
authors: N
authors: La Monica
authors: 6 IRCCS National Cancer Institute "G. Pascale ," Naples, Italy .
authors: Gennaro
authors: G
authors: Ciliberto
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D014614:Vaccines, Synthetic