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.

• Authors: 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
• Journal: British journal of cancer (Br J Cancer) Vol. 115 Issue 8 Pg. 940-948 (10 11 2016) ISSN: 1532-1827 [Electronic] England
• PMID: 27575850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Interleukin-3
• Receptors, Erythropoietin
• Receptors, Interleukin-3
• Recombinant Fusion Proteins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Bevacizumab
• KDR protein, human
• Kdr protein, mouse
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Angiogenesis Inhibitors (blood, pharmacology, therapeutic use)
• Animals
• B-Lymphocytes (drug effects)
• Bevacizumab (blood, pharmacology, therapeutic use)
• Biological Assay
• Cell Division
• Cell Line
• Enzyme-Linked Immunosorbent Assay
• Interleukin-3 (pharmacology)
• Mice
• Neoplasms (blood, drug therapy)
• Receptors, Erythropoietin (genetics)
• Receptors, Interleukin-3 (physiology)
• Recombinant Fusion Proteins (drug effects, genetics)
• Reproducibility of Results
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, blood, pharmacology)
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors, genetics, immunology)