Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma
Highly sensitive reporter-gene assays have been developed that allow both the direct vascular endothelial growth factor (VEGF) neutralizing activity of bevacizumab and the ability of bevacizumab to activate antibody dependent cellular cytotoxicity (ADCC) to be quantified rapidly and in a highly spec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.515556/full |
| _version_ | 1819207106626060288 |
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| author | Christophe Lallemand Rosa Ferrando-Miguel Michael Auer Sarah Iglseder Theresa Czech Anouk Gaber-Wagener Franziska Di Pauli Florian Deisenhammer Michael G. Tovey |
| author_facet | Christophe Lallemand Rosa Ferrando-Miguel Michael Auer Sarah Iglseder Theresa Czech Anouk Gaber-Wagener Franziska Di Pauli Florian Deisenhammer Michael G. Tovey |
| author_sort | Christophe Lallemand |
| collection | DOAJ |
| description | Highly sensitive reporter-gene assays have been developed that allow both the direct vascular endothelial growth factor (VEGF) neutralizing activity of bevacizumab and the ability of bevacizumab to activate antibody dependent cellular cytotoxicity (ADCC) to be quantified rapidly and in a highly specific manner. The use of these assays has shown that in 46 patients with ovarian cancer following four cycle of bevacizumab treatment, and in longitudinal samples from the two patients that respond to bevacizumab therapy from a small cohort of patients with glioblastoma, that there is a reasonably good correlation between bevacizumab drug levels determined by ELISA and bevacizumab activity, determined using either the VEGF-responsive reporter gene, or the ADCC assays. One of the two primary non-responders with glioblastoma exhibited high levels of ADCC activity suggesting reduced bevacizumab Fc engagement in vivo in contrast to the other primary non-responder, and the two secondary non-responders with a decreasing bevacizumab PK profile, determined by ELISA that exhibited low to undetectable ADCC activity. Drug levels were consistently higher than bevacizumab activity determined using the reporter gene assay in serial samples from one of the secondary non-responders and lower in some samples from the other secondary non-responder and ADCC activity was markedly lower in all samples from these patients suggesting that bevacizumab activity may be partially neutralized by anti-drug neutralizing antibodies (NAbs). These results suggest that ADCC activity may be correlated with the ability of some patients to respond to treatment with bevacizumab while the use of the VEGF-responsive reporter-gene assay may allow the appearance of anti-bevacizumab NAbs to be used as a surrogate maker of treatment failure prior to the clinical signs of disease progression. |
| first_indexed | 2024-12-23T05:18:13Z |
| format | Article |
| id | doaj.art-fa27d00b517643a3bae672aa94686f2a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T05:18:13Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fa27d00b517643a3bae672aa94686f2a2022-12-21T17:58:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.515556515556Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or GlioblastomaChristophe Lallemand0Rosa Ferrando-Miguel1Michael Auer2Sarah Iglseder3Theresa Czech4Anouk Gaber-Wagener5Franziska Di Pauli6Florian Deisenhammer7Michael G. Tovey8Svar Life Science France, Villejuif, FranceSvar Life Science France, Villejuif, FranceDepartment of Neurology, Innsbruck Medical University, Innsbruck, AustriaDepartment of Neurology, Innsbruck Medical University, Innsbruck, AustriaDepartment of Gynecology, Innsbruck Medical University, Innsbruck, AustriaDepartment of Gynecology, Innsbruck Medical University, Innsbruck, AustriaDepartment of Neurology, Innsbruck Medical University, Innsbruck, AustriaDepartment of Neurology, Innsbruck Medical University, Innsbruck, AustriaSvar Life Science France, Villejuif, FranceHighly sensitive reporter-gene assays have been developed that allow both the direct vascular endothelial growth factor (VEGF) neutralizing activity of bevacizumab and the ability of bevacizumab to activate antibody dependent cellular cytotoxicity (ADCC) to be quantified rapidly and in a highly specific manner. The use of these assays has shown that in 46 patients with ovarian cancer following four cycle of bevacizumab treatment, and in longitudinal samples from the two patients that respond to bevacizumab therapy from a small cohort of patients with glioblastoma, that there is a reasonably good correlation between bevacizumab drug levels determined by ELISA and bevacizumab activity, determined using either the VEGF-responsive reporter gene, or the ADCC assays. One of the two primary non-responders with glioblastoma exhibited high levels of ADCC activity suggesting reduced bevacizumab Fc engagement in vivo in contrast to the other primary non-responder, and the two secondary non-responders with a decreasing bevacizumab PK profile, determined by ELISA that exhibited low to undetectable ADCC activity. Drug levels were consistently higher than bevacizumab activity determined using the reporter gene assay in serial samples from one of the secondary non-responders and lower in some samples from the other secondary non-responder and ADCC activity was markedly lower in all samples from these patients suggesting that bevacizumab activity may be partially neutralized by anti-drug neutralizing antibodies (NAbs). These results suggest that ADCC activity may be correlated with the ability of some patients to respond to treatment with bevacizumab while the use of the VEGF-responsive reporter-gene assay may allow the appearance of anti-bevacizumab NAbs to be used as a surrogate maker of treatment failure prior to the clinical signs of disease progression.https://www.frontiersin.org/article/10.3389/fimmu.2020.515556/fullbevacizumabADCCglioblastomaovarian cancerVEGFbioassay |
| spellingShingle | Christophe Lallemand Rosa Ferrando-Miguel Michael Auer Sarah Iglseder Theresa Czech Anouk Gaber-Wagener Franziska Di Pauli Florian Deisenhammer Michael G. Tovey Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma Frontiers in Immunology bevacizumab ADCC glioblastoma ovarian cancer VEGF bioassay |
| title | Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma |
| title_full | Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma |
| title_fullStr | Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma |
| title_full_unstemmed | Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma |
| title_short | Quantification of Bevacizumab Activity Following Treatment of Patients With Ovarian Cancer or Glioblastoma |
| title_sort | quantification of bevacizumab activity following treatment of patients with ovarian cancer or glioblastoma |
| topic | bevacizumab ADCC glioblastoma ovarian cancer VEGF bioassay |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.515556/full |
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