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
2011 Impact Factor: 2.203
2011 SCImago Journal Rankings: 0.302
DOIhttp://dx.doi.org/10.1016/S0022-1759(03)00071-1
ISI Accession Number IDWOS:000183661800015
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 2.203
2011 SCImago Journal Rankings: 0.302
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
Author Affiliations
  1. The University of Hong Kong
  2. Imperial College London