UMMS Affiliation

MassBiologics

Publication Date

2016-04-05

Document Type

Article

Disciplines

Immunology and Infectious Disease | Surgical Procedures, Operative

Abstract

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.

DOI of Published Version

10.1038/ncomms11138

Source

Nat Commun. 2016 Apr 5;7:11138. doi: 10.1038/ncomms11138. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Comments

Full author list omitted for brevity. For full list of authors see article.

Related Resources

Link to Article in PubMed

PubMed ID

27045379

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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