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A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer.
- 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]
- Subjects :
- VASCULAR endothelial growth factor antagonists
B cells
BIOLOGICAL assay
CELL division
CELL lines
CELL receptors
ENZYME-linked immunosorbent assay
INTERLEUKIN-3
NEOVASCULARIZATION inhibitors
RECOMBINANT proteins
RESEARCH evaluation
TUMORS
VASCULAR endothelial growth factors
PHARMACODYNAMICS
THERAPEUTICS
CELL physiology
Subjects
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