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

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.

journal_name

Br J Cancer

authors

Wentink MQ,Broxterman HJ,Lam SW,Boven E,Walraven M,Griffioen AW,Pili R,van der Vliet HJ,de Gruijl TD,Verheul HM

doi

10.1038/bjc.2016.275

subject

Has Abstract

pub_date

2016-10-11 00:00:00

pages

940-948

issue

8

eissn

0007-0920

issn

1532-1827

pii

bjc2016275

journal_volume

115

pub_type

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