1. A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer.
- Author
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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, and Verheul, Henk M W
- 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 - Abstract
Background: 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.Methods: 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).Results: 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.Conclusions: 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]- Published
- 2016
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