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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
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TitleMammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4Ig) in milk by transgenesis
 
AuthorsLui, VCH1
Tam, PKH1
Leung, MYK1
Lau, JYB1
Chan, JKY1
Chan, VSF1
Dallman, M2
Cheah, KSE1
 
KeywordsCTLA4Ig
Immunosuppression
Milk
Transgenesis
Transplantation
 
Issue Date2003
 
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jim
 
CitationJournal Of Immunological Methods, 2003, v. 277 n. 1-2, p. 171-183 [How to Cite?]
DOI: http://dx.doi.org/10.1016/S0022-1759(03)00071-1
 
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.
 
ISSN0022-1759
2013 Impact Factor: 2.005
2013 SCImago Journal Rankings: 1.065
 
DOIhttp://dx.doi.org/10.1016/S0022-1759(03)00071-1
 
ISI Accession Number IDWOS:000183661800015
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLui, VCH
 
dc.contributor.authorTam, PKH
 
dc.contributor.authorLeung, MYK
 
dc.contributor.authorLau, JYB
 
dc.contributor.authorChan, JKY
 
dc.contributor.authorChan, VSF
 
dc.contributor.authorDallman, M
 
dc.contributor.authorCheah, KSE
 
dc.date.accessioned2011-03-28T09:25:27Z
 
dc.date.available2011-03-28T09:25:27Z
 
dc.date.issued2003
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Immunological Methods, 2003, v. 277 n. 1-2, p. 171-183 [How to Cite?]
DOI: http://dx.doi.org/10.1016/S0022-1759(03)00071-1
 
dc.identifier.doihttp://dx.doi.org/10.1016/S0022-1759(03)00071-1
 
dc.identifier.epage183
 
dc.identifier.hkuros76887
 
dc.identifier.isiWOS:000183661800015
 
dc.identifier.issn0022-1759
2013 Impact Factor: 2.005
2013 SCImago Journal Rankings: 1.065
 
dc.identifier.issue1-2
 
dc.identifier.pmid12799049
 
dc.identifier.scopuseid_2-s2.0-0038546813
 
dc.identifier.spage171
 
dc.identifier.urihttp://hdl.handle.net/10722/132499
 
dc.identifier.volume277
 
dc.languageeng
 
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jim
 
dc.publisher.placeNetherlands
 
dc.relation.ispartofJournal of Immunological Methods
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Immunological Methods. Copyright © Elsevier BV.
 
dc.subject.meshAnimals
 
dc.subject.meshAntigens, CD80 - immunology
 
dc.subject.meshCHO Cells
 
dc.subject.meshChromatography, Affinity
 
dc.subject.meshCricetinae
 
dc.subject.meshFemale
 
dc.subject.meshFlow Cytometry
 
dc.subject.meshHumans
 
dc.subject.meshImmunoconjugates - genetics - immunology - metabolism
 
dc.subject.meshImmunosuppressive Agents - immunology - isolation & purification - metabolism
 
dc.subject.meshLymphocyte Culture Test, Mixed
 
dc.subject.meshMammary Glands, Animal - immunology - metabolism - secretion
 
dc.subject.meshMice
 
dc.subject.meshMice, Transgenic
 
dc.subject.meshMilk - immunology - metabolism - secretion
 
dc.subject.meshRecombinant Proteins - genetics - immunology - metabolism
 
dc.subject.meshSwine
 
dc.subject.meshTransfection
 
dc.subjectCTLA4Ig
 
dc.subjectImmunosuppression
 
dc.subjectMilk
 
dc.subjectTransgenesis
 
dc.subjectTransplantation
 
dc.titleMammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (CTLA4Ig) in milk by transgenesis
 
dc.typeArticle
 
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<contributor.author>Chan, JKY</contributor.author>
<contributor.author>Chan, VSF</contributor.author>
<contributor.author>Dallman, M</contributor.author>
<contributor.author>Cheah, KSE</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. Imperial College London