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A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer.

Authors :
Wentink, Madelon Q
Broxterman, Henk J
Lam, Siu W
Boven, Epie
Walraven, Maudy
Griffioen, Arjan W
Pili, Roberto
van der Vliet, Hans J
de Gruijl, Tanja D
Verheul, Henk M W
Source :
British Journal of Cancer; 10/11/2016, Vol. 115 Issue 8, p940-948, 9p, 1 Diagram, 2 Charts, 2 Graphs
Publication Year :
2016

Abstract

<bold>Background: </bold>Only a small proportion of patients respond to anti-VEGF therapy, pressing the need for a reliable biomarker that can identify patients who will benefit. We studied the biological activity of anti-VEGF antibodies in patients' blood during anti-VEGF therapy by using the Ba/F3-VEGFR2 cell line, which is dependent on VEGF for its growth.<bold>Methods: </bold>Serum samples from 22 patients with cancer before and during treatment with bevacizumab were tested for their effect on proliferation of Ba/F3-VEGFR2 cells. Vascular endothelial growth factor as well as bevacizumab concentrations in serum samples from these patients were determined by enzyme linked immunosorbent assay (ELISA).<bold>Results: </bold>The hVEGF-driven cell proliferation was effectively blocked by bevacizumab (IC50 3.7 μg ml-1; 95% CI 1.7-8.3 μg ml-1). Cell proliferation was significantly reduced when patients' serum during treatment with bevacizumab was added (22-103% inhibition compared with pre-treatment). Although bevacizumab levels were not related, on-treatment serum VEGF levels were correlated with Ba/F3-VEGFR2 cell proliferation.<bold>Conclusions: </bold>We found that the neutralising effect of anti-VEGF antibody therapy on the biological activity of circulating VEGF can be accurately determined with a Ba/F3-VEGFR2 bioassay. The value of this bioassay to predict clinical benefit of anti-VEGF antibody therapy needs further clinical evaluation in a larger randomised cohort. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
115
Issue :
8
Database :
Complementary Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
118708042
Full Text :
https://doi.org/10.1038/bjc.2016.275