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dc.contributor.authorMohiuddin, Muhammad M.
dc.contributor.authorBelli, Aaron J.
dc.contributor.authorReimann, Keith A.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:42:17Z
dc.date.available2022-08-23T16:42:17Z
dc.date.issued2016-04-05
dc.date.submitted2016-10-05
dc.identifier.citationNat Commun. 2016 Apr 5;7:11138. doi: 10.1038/ncomms11138. <a href="http://dx.doi.org/10.1038/ncomms11138">Link to article on publisher's site</a>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/ncomms11138
dc.identifier.pmid27045379
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40062
dc.description<p>Full author list omitted for brevity. For full list of authors see article.</p>
dc.description.abstractPreventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and alphaCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed alphaCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of alphaCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27045379&dopt=Abstract">Link to Article in PubMed</a>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectImmunology and Infectious Disease
dc.subjectSurgical Procedures, Operative
dc.titleChimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume7
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3872&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2867
dc.identifier.contextkey9233087
refterms.dateFOA2022-08-23T16:42:17Z
html.description.abstract<p>Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and alphaCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed alphaCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of alphaCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days.</p>
dc.identifier.submissionpathoapubs/2867
dc.contributor.departmentMassBiologics
dc.source.pages11138


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