Development of a robust reporter-based assay for the bioactivity determination of anti-VEGF therapeutic antibodies

Wang, Lan; Xu, Gang; Gao, Kai; Wilkinson, Jennifer; Zhang, Feng; Yu, Lei; Liu, Chunyu; Yu, Chuanfei; Wang, Wenbo; Li, Meng; Chen, Wei; Fan, Frank; Cong, Mei; Wang, Junzhi

doi:10.1016/j.jpba.2016.03.042

Cited by 32 publications

(25 citation statements)

References 32 publications

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“…Several authors studied the inhibitory effects of bevacizumab on angiogenesis using cultured HUVEC in vitro 53, 54 . Thus, in our experience, the biological activity of bevacizumab was determined by its capacity to inhibit the HUVEC proliferation induced by VEGF 165 .…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in our experience, the biological activity of bevacizumab was determined by its capacity to inhibit the HUVEC proliferation induced by VEGF 165 . VEGF 165 was chosen because is the main isoform of VEGF-A that presents the most physiological relevant activity 54, 55 . For that reason, 50 ng/mL of VEGF was added at all the formulations 56 .…”

Section: Discussionmentioning

confidence: 99%

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A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles

Sousa

Cruz

Fonte

et al. 2017

Sci Rep

106

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Monoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance. In this work, we show a promising strategy of encapsulating bevacizumab to protect and deliver it, in a controlled manner, increasing the time between administrations and formulation shelf-life. Nanoencapsulation of bevacizumab represents a significant advance for selective antiangiogenic therapies since extracellular, cell surface and intracellular targets can be reached. The present study shows that bevacizumab-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles does not impair its native-like structure after encapsulation and fully retain the bioactivity, making this nanosystem a new paradigm for the improvement of angiogenic therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles

Sousa

Cruz

Fonte

et al. 2017

Sci Rep

106

View full text Add to dashboard Cite

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“…A reporter-based assay (Promega, Madison, WI, USA) for anti-VEGF antibodies was used to determine the biological activity of the spray-dried powders. Detailed information about the assay is available on Promega's website and in Wang et al [25]. In the VEGF bioassay, an engineered cell line (KDF/NFAT-RE HEK293) that expresses VEGF receptor-2 (VEGFR2/KDR) was used, combined with a VEGF-stimulated luciferase reporter.…”

Section: Activity Assaymentioning

confidence: 99%

Local Treatment of Non-small Cell Lung Cancer with a Spray-Dried Bevacizumab Formulation

et al. 2021

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Local delivery of biotherapeutics to the lung holds great promise for treatment of lung diseases, but development of physically stable, biologically active dry powder formulations of large molecules for inhalation has remained a challenge. Here, spray drying was used to manufacture a dry powder pulmonary formulation of bevacizumab, a monoclonal antibody approved to treat non-small cell lung cancer (NSCLC) by intravenous infusion. By reformulating bevacizumab for local delivery, reduced side effects, lower doses, and improved patient compliance are possible. The formulation had aerosol properties suitable for delivery to the deep lung, as well as good physical stability at ambient temperature for at least 6 months. Bevacizumab’s anti-VEGF bioactivity was not impacted by the manufacturing process. The formulation was efficacious in an in vivo rat model for NSCLC at a 10-fold decrease in dose relative to the intravenous control.

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“…Some of these assays have subsequently found their way into cell-based assays for drug development [14]. Characteristics of these assays include their ability to measure the regulation of cellular signalling events upon drug treatment instead of analyzing the respective downstream output processes such as proliferation, toxicity or cytokine release.…”

Section: Innovative Assay Formatsmentioning

confidence: 99%

Best Practices in Bioassay Development to Support Registration of Biopharmaceuticals

et al. 2019

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Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle.

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Development of a robust reporter-based assay for the bioactivity determination of anti-VEGF therapeutic antibodies

Cited by 32 publications

References 32 publications

A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles

A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles

Local Treatment of Non-small Cell Lung Cancer with a Spray-Dried Bevacizumab Formulation

Best Practices in Bioassay Development to Support Registration of Biopharmaceuticals

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