Binding characteristics and tumor targeting of a covalently linked divalent CC49 single-chain antibody
| العنوان: | Binding characteristics and tumor targeting of a covalently linked divalent CC49 single-chain antibody |
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| المؤلفون: | Barbara J.M. Booth, Surinder K. Batra, Guy W. Beresford, Gabriela Pavlinkova, David Colcher |
| المصدر: | International Journal of Cancer. 81:911-917 |
| بيانات النشر: | Wiley, 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Cancer Research, Biodistribution, Ratón, medicine.drug_class, Biology, Monoclonal antibody, medicine.disease_cause, High-performance liquid chromatography, Molecular biology, Divalent, Oncology, chemistry, Immunology, medicine, biology.protein, Antibody, Linker, Escherichia coli |
| الوصف: | Multivalency is a recognized means of increasing the functional affinity of single-chain Fvs (scFvs) for optimizing tumor uptake. A unique divalent single-chain Fv protein [sc(Fv)2], based on the variable regions of the monoclonal antibody (MAb) CC49, has been generated that differs from other dimeric single-chain constructs in that a linker sequence (L) is encoded between the repeated VL and VH domains (VL-L-VH-L-VL-L-VH). This construct was expressed in soluble form in Escherichia coli and purified by ion-exchange and gel-filtration chromatography. Purity and immunoreactivity were determined by SDS-PAGE, HPLC and competitive RIA. sc(Fv)2 exhibited a relative KA (3.34 × 107 M−1) similar to that of the native IgG (1.14 × 108 M−1) as determined by BIAcore analysis. Pharmacokinetic studies showed rapid blood clearance for sc(Fv)2, with a T1/2 less than 40 min. Whole-body clearance analysis also revealed rapid clearance, suggesting no significant retention in the extravascular space or normal tissues. Biodistribution studies of radiolabeled sc(Fv)2 showed tumor uptake greater than 6% ID/g after 30 min, which remained at this level for 6 hr. High tumor uptake and retention of sc(Fv)2 coupled with rapid blood and whole-body clearance makes this dimeric scFv of MAb CC49 a strong candidate for imaging and therapeutic applications. Int. J. Cancer 81:911–917, 1999. © 1999 Wiley-Liss, Inc. |
| تدمد: | 1097-0215 0020-7136 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c3da35ff3fb4d3e5b3f71fd5c0d363a1 https://doi.org/10.1002/(sici)1097-0215(19990611)81:6<911::aid-ijc12>3.0.co;2-o |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........c3da35ff3fb4d3e5b3f71fd5c0d363a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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