Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.575584
Title: Validation and identification of tumour endothelial markers and their uses in cancer vaccine
Author: Zhuang, Xiaodong
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2013
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Abstract:
The abnormal tumour microenvironment, which is typically hypoxic, acidic and with poor blood flow, induces the endothelial expression of genes not found on normal microvessels. By selectively targeting these tumour endothelial markers (TEMs) it is possible to induce tumour regression, presenting a potential strategy for therapeutic intervention. Potential TEMs were predicted by bioinformatics data mining. Validation of these TEM candidates identified a novel TEM CLEC14A. Functional characterization suggests a regulatory role of CLEC14A in endothelial cell migration. Inhibition of endothelial migration by CLEC14A antisera or monoclonal antibody holds therapeutic promise for the treatment of cancer. Differential gene expression analysis of freshly isolated lung tumour endothelium by 2nd generation sequencing identified 13 putative TEMs. Subsequent validation work confirmed six of which to be expressed on lung tumour vasculature. Finally, a pre-validated marker, Robo4, was investigated as a cancer vaccine. A strong antibody response was induced by delivery of pure mouse Robo4 protein or a Robo4 conjugate. The in vivo sponge assay in Robo4 vaccinated mice showed a significant reduction in vessel invasion. Tumour implantation experiments in vaccinated mice showed a marked delay in tumour growth.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.575584  DOI: Not available
Keywords: QR180 Immunology ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)
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