Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes

Benjamin J. Burwitz, Helen L. Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W. Legasse, Katherine B. Hammond, Stephanie L. Junell, Jason S. Reed, Benjamin N. Bimber, Justin M. Greene, Gabriela M. Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K. Axthelm, Rebecca Ducore, Anne Lewis, Lois M.A. ColginTheodore Hobbs, Lauren D. Martin, Betsy Ferguson, Charles R. Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J. Stanton, Richard T. Maziarz, Jonah B. Sacha

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 multi-lineage, full donor chimerism and recipient-specific tolerance while maintaining pathogen-specific 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.

Original languageEnglish (US)
Article number1418
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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