title: A functional bioassay to determine the activity of anti-VEGF antibody therapy in blood of patients with cancer.
abstract: 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.
  
  
  
  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).
  
  
  
  The hVEGF-driven cell proliferation was effectively blocked by bevacizumab (IC503.7 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.
  
  
  
  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: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Madelon Q
authors: MQ
authors: Wentink
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Henk J
authors: HJ
authors: Broxterman
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Siu W
authors: SW
authors: Lam
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Epie
authors: E
authors: Boven
authors: Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands.
authors: Maudy
authors: M
authors: Walraven
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Arjan W
authors: AW
authors: Griffioen
authors: Department of Hematology/Oncology, Indiana University, Indianapolis, Indiana.
authors: Roberto
authors: R
authors: Pili
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Hans J
authors: HJ
authors: van der Vliet
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Tanja D
authors: TD
authors: de Gruijl
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Henk M W
authors: HM
authors: Verheul
mesh_terms: D020533:Angiogenesis Inhibitors / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D000068258:Bevacizumab / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D001681:Biological Assay; D002455:Cell Division; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D017467:Receptors, Erythropoietin / Q000235:genetics; D016185:Receptors, Interleukin-3 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics; D015203:Reproducibility of Results; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D007377:Interleukin-3; D017467:Receptors, Erythropoietin; D016185:Receptors, Interleukin-3; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C000588866:KDR protein, human; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2