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 (IC 50 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.
Original language | English (US) |
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Pages (from-to) | 940-948 |
Number of pages | 9 |
Journal | British Journal of Cancer |
Volume | 115 |
Issue number | 8 |
DOIs | |
State | Published - Oct 11 2016 |
Externally published | Yes |
Keywords
- angiogenesis
- antibody
- bevacizumab
- bioassay
- proliferation assay
- VEGF
ASJC Scopus subject areas
- Oncology
- Cancer Research