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

Madelon Q. Wentink, Henk J. Broxterman, Siu W. Lam, Epie Boven, Maudy Walraven, Arjan W. Griffioen, Roberto Pili, Hans J. Van Der Vliet, Tanja D. De Gruijl, Henk M W Verheul

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish (US)
Pages (from-to)940-948
Number of pages9
JournalBritish Journal of Cancer
Volume115
Issue number8
DOIs
StatePublished - Oct 11 2016

Fingerprint

Biological Assay
Vascular Endothelial Growth Factor A
Anti-Idiotypic Antibodies
Neoplasms
Therapeutics
Cell Proliferation
Serum
Biological Therapy
Biomarkers
Enzyme-Linked Immunosorbent Assay
Bevacizumab
Cell Line
Growth

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wentink, M. Q., Broxterman, H. J., Lam, S. W., Boven, E., Walraven, M., Griffioen, A. W., ... Verheul, H. M. W. (2016). A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer. British Journal of Cancer, 115(8), 940-948. https://doi.org/10.1038/bjc.2016.275

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

In: British Journal of Cancer, Vol. 115, No. 8, 11.10.2016, p. 940-948.

Research output: Contribution to journalArticle

Wentink, MQ, Broxterman, HJ, Lam, SW, Boven, E, Walraven, M, Griffioen, AW, Pili, R, Van Der Vliet, HJ, De Gruijl, TD & Verheul, HMW 2016, 'A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer', British Journal of Cancer, vol. 115, no. 8, pp. 940-948. https://doi.org/10.1038/bjc.2016.275
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. / A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer. In: British Journal of Cancer. 2016 ; Vol. 115, No. 8. pp. 940-948.
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AU - Lam, Siu W.

AU - Boven, Epie

AU - Walraven, Maudy

AU - Griffioen, Arjan W.

AU - Pili, Roberto

AU - Van Der Vliet, Hans J.

AU - De Gruijl, Tanja D.

AU - Verheul, Henk M W

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AB - 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.

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