Robo4 vaccines induce antibodies that retard tumor growth

Xiaodong Zhuang, Forhad Ahmed, Yang Zhang, Henry Ferguson, Jane C Steele, Neil M Steven, Zsuzsanna Nagy, Victoria L Heath, Kai-Michael Toellner, Roy Bicknell

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10 Citations (Scopus)
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Abstract

Tumor endothelial specific expression of Robo4 in adults identifies this plasma membrane protein as an anti-cancer target for immunotherapeutic approaches, such as vaccination. In this report, we describe how vaccination against Robo4 inhibits angiogenesis and tumor growth. To break tolerance to the auto-antigen Robo4, mice were immunised with the extracellular domain of mouse Robo4, fused to the Fc domain of human immunoglobulin within an adjuvant. Vaccinated mice show a strong antibody response to Robo4, with no objectively detectable adverse effects on health. Robo4 vaccinated mice showed impaired fibrovascular invasion and angiogenesis in a rodent sponge implantation assay, as well as a reduced growth of implanted syngeneic Lewis lung carcinoma. The anti-tumor effect of Robo4 vaccination was present in CD8 deficient mice but absent in B cell or IgG1 knockout mice, suggesting antibody dependent cell mediated cytotoxicity as the anti-vascular/anti-tumor mechanism. Finally, we show that an adjuvant free soluble Robo4-carrier conjugate can retard tumor growth in carrier primed mice. These results point to appropriate Robo4 conjugates as potential anti-angiogenic vaccines for cancer patients.

Original languageEnglish
Pages (from-to)83-95
Number of pages13
JournalAngiogenesis
Volume18
Issue number1
Early online date28 Oct 2014
DOIs
Publication statusPublished - Jan 2015

Keywords

  • Immunotherapy
  • Conjugate vaccines
  • ADCC
  • Cancer

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