کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8551339 | 1562107 | 2018 | 46 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab
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کلمات کلیدی
i.v.VEGF165HPDBiosimilarHUVECCmaxAUC - AUCantidrug antibody - آنتی بادی ضد سرطانbevacizumab - بواسیزومابToxicokinetics - تاکسیکوسینتیک، تاکسیکوکینتیکEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاmaximum serum concentration - حداکثر غلظت سرمیIntravenous - داخل وریدیHuman umbilical vein endothelial cells - سلول های اندوتلیالی ورید ناف انسانNonclinical - غیر کلاسیکVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)Sprague Dawley rat - موش Sprague Dawleycynomolgus monkey - میمون cynomolgusADA - وجود دارد
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab](/preview/png/8551339.png)
چکیده انگلیسی
Bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney cancer, and glioblastoma. To support clinical development of the potential bevacizumab biosimilar PF-06439535, nonclinical studies evaluated structural, functional, toxicological, and toxicokinetic similarity to bevacizumab sourced from the European Union (bevacizumab-EU) and United States (bevacizumab-US). Peptide mapping demonstrated the amino acid sequence of PF-06439535 was identical to bevacizumab-EU and bevacizumab-US. Biologic activity, measured via inhibition of VEGF-induced cell proliferation in human umbilical vein endothelial cells and binding to VEGF isoforms, was similar across the three drugs. In vivo similarity was demonstrated in cynomolgus monkeys administered intravenous PF-06439535 or bevacizumab-EU (0 or 10â¯mg/kg/dose twice weekly for 1 month; total of nine doses). Systemic exposure appeared similar and test article-related effects were limited to physeal dysplasia of the distal femur. The potential for non-target-mediated toxicity of PF-06439535 was evaluated in rats administered intravenous PF-06439535 (15 or 150â¯mg/kg/dose twice weekly for 15 days; total of five doses). Nonadverse higher liver weights and minimal sinusoidal cell hyperplasia were observed. Collectively, these studies demonstrated similarity of PF-06439535 to bevacizumab, supporting entry into clinical development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 95, June 2018, Pages 236-243
Journal: Regulatory Toxicology and Pharmacology - Volume 95, June 2018, Pages 236-243
نویسندگان
Marjorie A. Peraza, Karen E. Rule, Michael H.I. Shiue, Gregory L. Finch, Stéphane Thibault, Paul R. Brown, David W. Clarke, Michael W. Leach,