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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 (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 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. Social Bookmarking                   What's this? Submitted December 9, 2002 Accepted March 31, 2003 Synergy between tumor immunotherapy and anti-angiogenic therapy Smita Nair, David Boczkowski, Benjamin Moeller, Mark Dewhirst, Johannes Vieweg, and Eli Gilboa* Department of Surgery, Duke University Medical Center, Durham, NC, USA Department of Pathology, Duke University Medical Center, Durham, NC, USA Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA Department of Urology, Duke University Medical Center, Durham, NC, USA * Corresponding author; email: e.gilboa{at}cgct.duke.edu. This study tested the hypothesis that combination of anti-angiogenic therapy and tumor immunotherapy of cancer are synergistic. To inhibit angiogenesis, mice were immunized with dendritic cells (DC) transfected with mRNA encoding products which 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 CTL responses and led to partial inhibition of angiogenesis. Anti-angiogenic 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. Co-immunization of mice against VEGFR-2 or Tie2 and total tumor RNA exhibited a synergistic antitumor effect. Synergism was also observed when mice were co-immunized with various combinations of defined tumor-expressed antigens, telomerase reverse transcriptase (TERT) or TRP-2, and VEGF or VEGFR-2. This study shows that co-immunizing mice against angiogenesis-associated and tumor-expressed antigens can deliver two 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: S.-i. Fujii, A. Goto, and K. Shimizu Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand confer antitumor immunity Blood, April 30, 2009; 113(18): 4262 - 4272. [Abstract] [Full Text] [PDF] M. Z. Noman, S. Buart, J. Van Pelt, C. Richon, M. Hasmim, N. Leleu, W. M. Suchorska, A. Jalil, Y. Lecluse, F. El Hage, et al. 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