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Article: Mammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4Ig) in milk by transgenesis

TitleMammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4Ig) in milk by transgenesis
Authors
KeywordsCTLA4Ig
Immunosuppression
Milk
Transgenesis
Transplantation
Issue Date2003
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jim
Citation
Journal Of Immunological Methods, 2003, v. 277 n. 1-2, p. 171-183 How to Cite?
Abstract
A major challenge in the field of transplantation is to prevent graft rejection and prolong graft survival. Tolerance induction is a promising way to achieve long-term graft survival without the need for potent immunosuppression and its associated side effects. The recent success of co-stimulatory blockade by the chimeric protein CTLA4Ig in the modulation of the recipient's immune system and the prolongation of graft survival in animal models suggests a possible application of CTLA4Ig in clinical transplantation. To produce sufficient amounts of CTLA4Ig for future clinical application, we sought to use the mammary gland as a bioreactor and produce CTLA4Ig in the milk of transgenic farm animals. Prior to the generation of transgenic farm animals, we tested our strategy in mice. Using the promoter of the sheep β-lactoglobulin gene, we expressed our CTLA4Ig chimeric gene in the mammary gland of transgenic mice. The yield of CTLA4Ig was fivefold higher in transgenic milk than that from transfected cells. Purified milk-derived CTLA4Ig is biologically active and suppresses T cell activation. We showed that the production of CTLA4Ig in the milk has no adverse immunosuppression effect on the transgenic animals and the offsprings that were fed with the transgenic milk. The findings suggest that the approach to produce CTLA4Ig in milk by transgenesis is feasible; further studies involving farm animals are warranted. © 2003 Elsevier Science B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/132499
ISSN
2013 Impact Factor: 2.005
2013 SCImago Journal Rankings: 1.065
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong
  2. Imperial College London
DC FieldValueLanguage
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorLeung, MYKen_HK
dc.contributor.authorLau, JYBen_HK
dc.contributor.authorChan, JKYen_HK
dc.contributor.authorChan, VSFen_HK
dc.contributor.authorDallman, Men_HK
dc.contributor.authorCheah, KSEen_HK
dc.date.accessioned2011-03-28T09:25:27Z-
dc.date.available2011-03-28T09:25:27Z-
dc.date.issued2003en_HK
dc.identifier.citationJournal Of Immunological Methods, 2003, v. 277 n. 1-2, p. 171-183en_HK
dc.identifier.issn0022-1759en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132499-
dc.description.abstractA major challenge in the field of transplantation is to prevent graft rejection and prolong graft survival. Tolerance induction is a promising way to achieve long-term graft survival without the need for potent immunosuppression and its associated side effects. The recent success of co-stimulatory blockade by the chimeric protein CTLA4Ig in the modulation of the recipient's immune system and the prolongation of graft survival in animal models suggests a possible application of CTLA4Ig in clinical transplantation. To produce sufficient amounts of CTLA4Ig for future clinical application, we sought to use the mammary gland as a bioreactor and produce CTLA4Ig in the milk of transgenic farm animals. Prior to the generation of transgenic farm animals, we tested our strategy in mice. Using the promoter of the sheep β-lactoglobulin gene, we expressed our CTLA4Ig chimeric gene in the mammary gland of transgenic mice. The yield of CTLA4Ig was fivefold higher in transgenic milk than that from transfected cells. Purified milk-derived CTLA4Ig is biologically active and suppresses T cell activation. We showed that the production of CTLA4Ig in the milk has no adverse immunosuppression effect on the transgenic animals and the offsprings that were fed with the transgenic milk. The findings suggest that the approach to produce CTLA4Ig in milk by transgenesis is feasible; further studies involving farm animals are warranted. © 2003 Elsevier Science B.V. All rights reserved.en_HK
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jimen_HK
dc.relation.ispartofJournal of Immunological Methodsen_HK
dc.rightsJournal of Immunological Methods. Copyright © Elsevier BV.-
dc.subjectCTLA4Igen_HK
dc.subjectImmunosuppressionen_HK
dc.subjectMilken_HK
dc.subjectTransgenesisen_HK
dc.subjectTransplantationen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntigens, CD80 - immunologyen_HK
dc.subject.meshCHO Cellsen_HK
dc.subject.meshChromatography, Affinityen_HK
dc.subject.meshCricetinaeen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunoconjugates - genetics - immunology - metabolismen_HK
dc.subject.meshImmunosuppressive Agents - immunology - isolation & purification - metabolismen_HK
dc.subject.meshLymphocyte Culture Test, Mixeden_HK
dc.subject.meshMammary Glands, Animal - immunology - metabolism - secretionen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshMilk - immunology - metabolism - secretionen_HK
dc.subject.meshRecombinant Proteins - genetics - immunology - metabolismen_HK
dc.subject.meshSwineen_HK
dc.subject.meshTransfectionen_HK
dc.titleMammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4Ig) in milk by transgenesisen_HK
dc.typeArticleen_HK
dc.identifier.emailLui, VCH:vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH:paultam@hkucc.hku.hken_HK
dc.identifier.emailChan, VSF:sfvchan@hku.hken_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authorityChan, VSF=rp01459en_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0022-1759(03)00071-1en_HK
dc.identifier.pmid12799049en_HK
dc.identifier.scopuseid_2-s2.0-0038546813en_HK
dc.identifier.hkuros76887-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0038546813&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume277en_HK
dc.identifier.issue1-2en_HK
dc.identifier.spage171en_HK
dc.identifier.epage183en_HK
dc.identifier.isiWOS:000183661800015-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridLeung, MYK=8766283100en_HK
dc.identifier.scopusauthoridLau, JYB=8766283200en_HK
dc.identifier.scopusauthoridChan, JKY=15730226000en_HK
dc.identifier.scopusauthoridChan, VSF=35200370000en_HK
dc.identifier.scopusauthoridDallman, M=35473592200en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK

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