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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 publication

DOI

10.1007/s10456-014-9448-z

Type

Journal article

Journal

Angiogenesis

Publication Date

01/2015

Volume

18

Pages

83 - 95

Addresses

Institute for Biomedical Research, Schools of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

Keywords

Tumor Cells, Cultured, Animals, Mice, Inbred C57BL, Humans, Mice, Neoplasms, Neovascularization, Pathologic, Papain, Receptors, Immunologic, Nerve Tissue Proteins, Vaccines, Synthetic, DNA Primers, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Immunotherapy, Chromatography, Affinity, Immunohistochemistry, Polymerase Chain Reaction, Amino Acid Sequence, Genetic Vectors, Molecular Sequence Data, Adult, Immunoglobulin Fc Fragments, HEK293 Cells