This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hodge, J. W. Articles by Schlom, J. Search for Related Content PubMed PubMed Citation Articles by Hodge, J. W. Articles by Schlom, J.

Modified Vaccinia Virus Ankara Recombinants Are as Potent as Vaccinia Recombinants in Diversified Prime and Boost Vaccine Regimens to Elicit Therapeutic Antitumor Responses

¹ Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland,
² Therion Biologics Corporation, Cambridge, Massachusetts

Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7–1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4⁺ and CD8⁺ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naïve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4⁺ and CD8⁺ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.

This article has been cited by other articles:

				K. W. Hance, C. J. Rogers, D. A. Zaharoff, D. Canter, J. Schlom, and J. W. Greiner The Antitumor and Immunoadjuvant Effects of IFN-{alpha} in Combination with Recombinant Poxvirus Vaccines Clin. Cancer Res., April 1, 2009; 15(7): 2387 - 2396. [Abstract] [Full Text] [PDF]

				T. I. Naslund, C. Uyttenhove, E. K. L. Nordstrom, D. Colau, G. Warnier, M. Jondal, B. J. Van den Eynde, and P. Liljestrom Comparative Prime-Boost Vaccinations Using Semliki Forest Virus, Adenovirus, and ALVAC Vectors Demonstrate Differences in the Generation of a Protective Central Memory CTL Response against the P815 Tumor J. Immunol., June 1, 2007; 178(11): 6761 - 6769. [Abstract] [Full Text] [PDF]

				C. Palena, K. A. Foon, D. Panicali, A. G. Yafal, J. Chinsangaram, J. W. Hodge, J. Schlom, and K. Y. Tsang Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules Blood, November 15, 2005; 106(10): 3515 - 3523. [Abstract] [Full Text] [PDF]

				Y. Huang, R. Fayad, A. Smock, A. M. Ullrich, and L. Qiao Induction of Mucosal and Systemic Immune Responses against Human Carcinoembryonic Antigen by an Oral Vaccine Cancer Res., August 1, 2005; 65(15): 6990 - 6999. [Abstract] [Full Text] [PDF]

				R. Bos, S. van Duikeren, T. van Hall, P. Kaaijk, R. Taubert, B. Kyewski, L. Klein, C. J.M. Melief, and R. Offringa Expression of a Natural Tumor Antigen by Thymic Epithelial Cells Impairs the Tumor-Protective CD4+ T-Cell Repertoire Cancer Res., July 15, 2005; 65(14): 6443 - 6449. [Abstract] [Full Text] [PDF]

				K. Y. Tsang, C. Palena, J. Yokokawa, P. M. Arlen, J. L. Gulley, G. P. Mazzara, L. Gritz, A. Gomez Yafal, S. Ogueta, P. Greenhalgh, et al. Analyses of Recombinant Vaccinia and Fowlpox Vaccine Vectors Expressing Transgenes for Two Human Tumor Antigens and Three Human Costimulatory Molecules Clin. Cancer Res., February 15, 2005; 11(4): 1597 - 1607. [Abstract] [Full Text] [PDF]

				A. Saha, S. K. Chatterjee, K. A. Foon, F. J. Primus, S. Sreedharan, K. Mohanty, and M. Bhattacharya-Chatterjee Dendritic Cells Pulsed with an Anti-Idiotype Antibody Mimicking Carcinoembryonic Antigen (CEA) Can Reverse Immunological Tolerance to CEA and Induce Antitumor Immunity in CEA Transgenic Mice Cancer Res., July 15, 2004; 64(14): 4995 - 5003. [Abstract] [Full Text] [PDF]