Targeting tumor-associated endothelial cells: anti-VEGFR2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth

Clin Cancer Res. 2012 Jan 15;18(2):454-64. doi: 10.1158/1078-0432.CCR-11-1102. Epub 2011 Nov 7.


Purpose: Angiogenesis is a key process in tumor progression. By binding VEGF, VEGF receptor-2 (VEGFR2) is a main signaling transducer in tumor-associated angiogenesis. Accordingly, therapeutic approaches against the VEGF/VEGFR2 signaling axis have been designed. However, an efficient and specific chemotherapeutic targeting of tumor-associated endothelial cells has not yet been achieved.

Experimental design: We have employed anti-VEGFR2 antibodies covalently linked to pegylated liposomal doxorubicin (PLD) to specifically ablate tumor-associated endothelial cells in the Rip1Tag2 mouse model of insulinoma, in the MMTV-PyMT mouse model of breast cancer, and in the HT-29 human colon cancer xenograft transplantation model.

Results: In each model, anti-VEGFR2-targeted immunoliposomes (ILs) loaded with doxorubicin (anti-VEGFR2-ILs-dox) were superior in therapeutic efficacy to empty liposomes, empty anti-VEGFR2-ILs, antibodies alone, and PLD. Efficacy was similar to that of the oral VEGFR1, -2, and -3 inhibitor PTK787. Detailed histopathologic and molecular analysis revealed a strong antiangiogenic effect of anti-VEGFR2-ILs-dox, and the observed antiangiogenic therapy was significantly more efficient in reducing tumor burden in well-vascularized transgenic mouse models as compared with the less-vascularized xenograft model.

Conclusions: Anti-VEGFR2 ILs provide a highly efficient approach to selectively deplete VEGFR2-expressing tumor vasculature. They offer a novel and promising anticancer strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Apoptosis
  • Blood Vessels / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / pharmacology*
  • Doxorubicin / therapeutic use
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology
  • Female
  • Humans
  • Immunotoxins / pharmacology*
  • Immunotoxins / therapeutic use
  • Insulinoma / blood supply
  • Insulinoma / drug therapy*
  • Insulinoma / pathology
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Xenograft Model Antitumor Assays


  • Angiogenesis Inhibitors
  • Immunotoxins
  • Doxorubicin
  • Vascular Endothelial Growth Factor Receptor-2