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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-12-3738. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3738v1 102/3/964    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nair, S. Articles by Gilboa, E. Search for Related Content PubMed PubMed Citation Articles by Nair, S. Articles by Gilboa, E. Related Collections Hematopoiesis and Stem Cells Immunobiology Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 964-971 IMMUNOBIOLOGY Synergy between tumor immunotherapy and antiangiogenic therapy Smita Nair, David Boczkowski, Benjamin Moeller, Mark Dewhirst, Johannes Vieweg, and Eli Gilboa From the Center for Genetic and Cellular Therapies, Department of Surgery, and the Departments of Pathology, Radiation Oncology, and Urology, Duke University Medical Center, Durham, NC This study tested the hypothesis that combination of antiangiogenic therapy and tumor immunotherapy of cancer is synergistic. To inhibit angiogenesis, mice were immunized with dendritic cells (DCs) transfected with mRNA that encode products that are preferentially expressed during neoangiogenesis: vascular endothelial growth factor receptor-2 (VEGFR-2) and Tie2 expressed in proliferating endothelial cells, and vascular endothelial growth factor (VEGF) expressed in the angiogenic stroma as well as the tumor cells used in this study. Immunization of mice against VEGF or VEGFR-2 stimulated cytotoxic T lymphocyte (CTL) responses and led to partial inhibition of angiogenesis. Antiangiogenic immunity was not associated with morbidity or mortality except for a transient impact on fertility seen in mice immunized against VEGFR-2, but not VEGF. Tumor growth was significantly inhibited in mice immunized against VEGF, VEGFR-2, and Tie2, either before tumor challenge or in the setting of pre-existing disease in murine B16/F10.9 melanoma and MBT-2 bladder tumor models. Coimmunization of mice against VEGFR-2 or Tie2 and total tumor RNA exhibited a synergistic antitumor effect. Synergism was also observed when mice were coimmunized with various combinations of defined tumor-expressed antigens, telomerase reverse transcriptase (TERT) or TRP-2, and VEGF or VEGFR-2. This study shows that coimmunizing mice against angiogenesis-associated and tumor-expressed antigens can deliver 2 compatible and synergistic cancer treatment modalities via a common treatment, namely immunization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Sun, M. Song, E. Jager, C. Schwer, S. Stevanovic, S. Flindt, J. Karbach, X. D. Nguyen, D. Schadendorf, and K. Cichutek Human CD4+ T Lymphocytes Recognize a Vascular Endothelial Growth Factor Receptor-2-Derived Epitope in Association with HLA-DR Clin. Cancer Res., July 1, 2008; 14(13): 4306 - 4315. [Abstract] [Full Text] [PDF] B. Zhang, Y. Zhang, N. 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