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
Related Resources
PubMed ID
27045379
Repository Citation
Mohiuddin MM, Belli AJ, Reimann KA. (2016). Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Open Access Articles. https://doi.org/10.1038/ncomms11138. Retrieved from https://escholarship.umassmed.edu/oapubs/2867
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Full author list omitted for brevity. For full list of authors see article.