| First Author | Zhuang X | Year | 2015 |
| Journal | Angiogenesis | Volume | 18 |
| Issue | 1 | Pages | 83-95 |
| PubMed ID | 25348086 | Mgi Jnum | J:309637 |
| Mgi Id | MGI:6759058 | Doi | 10.1007/s10456-014-9448-z |
| Citation | Zhuang X, et al. (2015) Robo4 vaccines induce antibodies that retard tumor growth. Angiogenesis 18(1):83-95 |
| abstractText | 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. |
