A Multi-DNA Preventive Vaccine for p53/Neu-Driven Cancer Syndrome
| Autor: | Manuela Iezzi, Ml Penichet, P.-L. Lollini, C. De Giovanni, Luigi Aurisicchio, Giordano Nicoletti, Stefania Croci, Annalisa Murgo, Marina Fabbi, Annalisa Astolfi, Patrizia Nanni, Am Orengo, Augusto Amici, Agnese Antognoli, Lorena Landuzzi, Piero Musiani, Silvano Ferrini, A. Palladini |
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| Přispěvatelé: | C. De Giovanni, G. Nicoletti, A. Palladini, S. Croci, L. Landuzzi, A. Antognoli, A. Murgo, A. Astolfi, S. Ferrini, M. Fabbi, A.M. Orengo, A. Amici, M. L. Penichet, L. Aurisicchio, M. Iezzi, P. Musiani, P. Nanni, P.-L. Lollini. |
| Rok vydání: | 2009 |
| Předmět: |
Cytotoxicity
Immunologic Receptor ErbB-2 T cell medicine.medical_treatment Genetic enhancement Cancer immunoprevention Transfection Major histocompatibility complex Cancer Vaccines Salivary Glands Major Histocompatibility Complex Interferon-gamma Mice Mammary Glands Animal Neoplastic Syndromes Hereditary Interferon Vaccines DNA Genetics medicine Animals Molecular Biology biology Genetic Therapy Immunotherapy Interleukin-12 Isotype Rats medicine.anatomical_structure Immunoglobulin G Immunology biology.protein Cytokines Molecular Medicine Female Tumor Suppressor Protein p53 Antibody medicine.drug |
| Zdroj: | Human Gene Therapy. 20:453-464 |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | The highly aggressive cancer syndrome of female mice carrying a p53 knockout allele and a rat HER-2/neu (Neu) transgene (BALB-p53Neu) can be prevented by a cell vaccine presenting three components: Neu, interleukin (IL)-12 production, and allogeneic major histocompatibility complex (MHC) alleles (Triplex cell vaccine). Here we tested a second-generation Triplex DNA-based vaccine (Tri-DNA), consisting of the combination of three gene components (a transmembrane-extracellular domain fragment of the Neu gene, IL-12 genes, and the H-2D(q) allogeneic MHC gene), carried by separate plasmids. The Tri-DNA vaccine was at least as effective as the Triplex cell vaccine for cancer immunoprevention, giving a similar delay in the onset of mammary cancer and complete protection from salivary cancer. Both vaccines induced anti-Neu antibodies of the murine IgG2a isotype at similar levels. The Tri-DNA vaccine gave more restricted immunostimulation, consisting of a fully helper T cell type 1 (Th1)-polarized response, with effective production of interferon (IFN)-gamma in response to the vaccine but no spontaneous production, and no induction of anti-Neu IgG3 antibodies. On the other hand, the Triplex cell vaccine induced both Th1 and Th2 cytokines, a strong increase in spontaneous IFN-gamma production, and high levels of IgG3 antibodies recognizing Neu-positive syngeneic cells. In conclusion, the Tri-DNA vaccine is as effective as Triplex cell vaccine, exploiting a more restricted immune stimulation. |
| Databáze: | OpenAIRE |
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