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- Title
Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes.
- Authors
Burwitz, Benjamin J.; Wu, Helen L.; Abdulhaqq, Shaheed; Shriver-Munsch, Christine; Swanson, Tonya; Legasse, Alfred W.; Hammond, Katherine B.; Junell, Stephanie L.; Reed, Jason S.; Bimber, Benjamin N.; Greene, Justin M.; Webb, Gabriela M.; Northrup, Mina; Laub, Wolfram; Kievit, Paul; MacAllister, Rhonda; Axthelm, Michael K.; Ducore, Rebecca; Lewis, Anne; Colgin, Lois M. A.
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.- tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques. Anti-GvHD prophylaxis of tacrolimus, post-transplant cyclophosphamide, and CD28 blockade induces multilineage, full donor chimerism and recipient-specific tolerance while maintaining pathogenspecific immunity. These results establish a new preclinical allogeneic HSCT model for evaluation of GvHD prophylaxis and next-generation HSCT-mediated therapies for solid organ tolerance, cure of non-malignant hematological disease, and HIV reservoir clearance.
- Subjects
HEMATOPOIETIC stem cell transplantation; KRA; HEMATOLOGIC malignancies; GRAFT versus host disease; MACAQUES; STEM cell transplantation
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01631-z