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

作者：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^*

来源：British Journal of Cancer, 2016, 115(8): 940-948.

DOI：10.1038/bjc.2016.275

• bioassay
• VEGF
• bevacizumab
• proliferation assay
• angiogenesis
• antibody

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 mu g ml(-1); 95% CI 1.7-8.3 mu g 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.

• 出版日期2016-10-11