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| Blood 2003 Apr 10; [epub ahead of print] | Related Articles, Links |
Synergy between tumor immunotherapy and anti-angiogenic therapy.
Nair S, Boczkowski D, Moeller B, Dewhirst M, Vieweg J, Gilboa E.
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
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.
PMID: 12689940 [PubMed - as supplied by publisher]
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