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Expression and characterization of a novel single-chain anti-vascular endothelial growth factor antibody in the goat milk

dc.contributor.authorLeiva M.J
dc.contributor.authorParra N.C
dc.contributor.authorContreras M.A
dc.contributor.authorTavares K.C.S
dc.contributor.authorMacaya L
dc.contributor.authorMartins L
dc.contributor.authorGaudencio S
dc.contributor.authorHidalgo Á
dc.contributor.authorKozak R.P
dc.contributor.authorGonzález A
dc.contributor.authorSánchez O
dc.contributor.authorToledo J.R
dc.contributor.authorMontesino R.
dc.date.accessioned2022-09-14T14:33:44Z
dc.date.available2022-09-14T14:33:44Z
dc.date.created2021
dc.identifier.issn1681656
dc.identifier.urihttp://hdl.handle.net/11407/7459
dc.descriptionVascular endothelial growth factor (VEGF) has essential functions in angiogenesis, endothelial cell proliferation, migration, and tumor invasion. Different approaches have been developed to suppress tumor angiogenesis, which is considered a hallmark of cancer. Anti-VEGF monoclonal antibodies constitute an important strategy for cancer immunotherapy, which has been produced on several platforms. In this study, a novel single-chain anti-VEGF monoclonal antibody (scVEGFmAb) was produced in the goat mammary gland by adenoviral transduction. scVEGFmAb was purified by affinity chromatography. N-glycans were analyzed by exoglycosidase digestion and hydrophilic interaction ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry. The biological activity of scVEGFmAb was assessed by scratch and mouse aortic ring assays. scVEGFmAb was produced at 0.61 g/L in the goat milk, and its purification rendered 95 % purity. N-glycans attached to scVEGFmAb backbone were mainly neutral biantennary core fucosylated with Galβ1,4GlcNAc motif, and charged structures were capped with Neu5Ac and Neu5Gc. The chimeric molecule significantly prevented cell migration and suppressed microvessel sprouting. These results demonstrated for the first time the feasibility of producing an anti-VEGF therapeutic antibody in the milk of non-transgenic goats with the potential to counteract tumor angiogenesis. © 2021 Elsevier B.V.eng
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.isversionofhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85110170549&doi=10.1016%2fj.jbiotec.2021.06.025&partnerID=40&md5=81936b622de74abfa97582ffc944a9ae
dc.sourceJournal of Biotechnology
dc.titleExpression and characterization of a novel single-chain anti-vascular endothelial growth factor antibody in the goat milk
dc.typeArticle
dc.rights.accessrightsinfo:eu-repo/semantics/restrictedAccess
dc.publisher.programCiencias Básicas
dc.type.spaArtículo
dc.identifier.doi10.1016/j.jbiotec.2021.06.025
dc.subject.keywordAdenoviral transductioneng
dc.subject.keywordAngiogenesiseng
dc.subject.keywordCancereng
dc.subject.keywordMammary glandeng
dc.subject.keywordN-glycanseng
dc.subject.keywordVascular endothelial growth factoreng
dc.subject.keywordBioactivityeng
dc.subject.keywordCell cultureeng
dc.subject.keywordCell engineeringeng
dc.subject.keywordCell proliferationeng
dc.subject.keywordDiseaseseng
dc.subject.keywordElectrospray ionizationeng
dc.subject.keywordEndothelial cellseng
dc.subject.keywordHydrophilicityeng
dc.subject.keywordLiquid chromatographyeng
dc.subject.keywordMass spectrometryeng
dc.subject.keywordPolysaccharideseng
dc.subject.keywordPurificationeng
dc.subject.keywordTumorseng
dc.subject.keywordAdenoviral transductioneng
dc.subject.keywordAngiogenesiseng
dc.subject.keywordAnti-vascular endothelial growth factorseng
dc.subject.keywordEndothelial cell proliferationeng
dc.subject.keywordGoat's milkeng
dc.subject.keywordMammary glandeng
dc.subject.keywordN-glycaneng
dc.subject.keywordSingle chainseng
dc.subject.keywordTumor angiogenesiseng
dc.subject.keywordVascular endothelial growth factoreng
dc.subject.keywordMonoclonal antibodieseng
dc.relation.citationvolume338
dc.relation.citationstartpage52
dc.relation.citationendpage62
dc.publisher.facultyFacultad de Ciencias Básicas
dc.affiliationLeiva, M.J., Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationParra, N.C., Recombinant Biopharmaceuticals Laboratory, Department of Pharmacology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationContreras, M.A., Recombinant Biopharmaceuticals Laboratory, Department of Pharmacology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationTavares, K.C.S., Molecular and Developmental Biology Lab, Experimental Biology Centre (NUBEX), University of Fortaleza (UNIFOR), Fortaleza, CE, Brazil
dc.affiliationMacaya, L., Recombinant Biopharmaceuticals Laboratory, Department of Pharmacology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationMartins, L., Molecular and Developmental Biology Lab, Experimental Biology Centre (NUBEX), University of Fortaleza (UNIFOR), Fortaleza, CE, Brazil
dc.affiliationGaudencio, S., Molecular and Developmental Biology Lab, Experimental Biology Centre (NUBEX), University of Fortaleza (UNIFOR), Fortaleza, CE, Brazil
dc.affiliationHidalgo, Á., Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationKozak, R.P., Ludger Ltd, Culham Science Centre, Oxfordshire, United Kingdom
dc.affiliationGonzález, A., Recombinant Biopharmaceuticals Laboratory, Department of Pharmacology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile, Faculty of Basic Sciences, University of Medellin, Cra. 87 Nº 30-65, Medellin, Antioquia, Colombia
dc.affiliationSánchez, O., Recombinant Biopharmaceuticals Laboratory, Department of Pharmacology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationToledo, J.R., Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
dc.affiliationMontesino, R., Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, University of Concepcion, Victor Lamas 1290, P.O. Box 160C, Concepcion, Chile
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dc.identifier.reponamereponame:Repositorio Institucional Universidad de Medellín
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