Publication: Transplantation of T-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates
Issued Date
2020-01-01
Resource Type
ISSN
18732399
0301472X
0301472X
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2-s2.0-85095986934
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Mahidol University
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SCOPUS
Bibliographic Citation
Experimental Hematology. (2020)
Suggested Citation
Saritha S. D'Souza, Sarah Bennett, Akhilesh Kumar, Laurel E. Kelnhofer, Jason Weinfurter, Kran Suknuntha, Jennifer Coonen, Andres Mejia, Heather Simmons, Thaddeus Golos, Peiman Hematti, Christian M. Capitini, Matthew R. Reynolds, Igor I. Slukvin Transplantation of T-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates. Experimental Hematology. (2020). doi:10.1016/j.exphem.2020.09.198 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/60419
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Title
Transplantation of T-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates
Other Contributor(s)
University of Wisconsin-Madison
University of Wisconsin School of Medicine and Public Health
University of Wisconsin School of Veterinary Medicine
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
University of Wisconsin Carbone Cancer Center
University of Wisconsin Hospital and Clinics
Wisconsin National Primate Research Center
University of Wisconsin School of Medicine and Public Health
University of Wisconsin School of Veterinary Medicine
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
University of Wisconsin Carbone Cancer Center
University of Wisconsin Hospital and Clinics
Wisconsin National Primate Research Center
Abstract
© 2020 ISEH – Society for Hematology and Stem Cells Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for hematologic cancers and chronic infections such as human immunodeficiency virus (HIV). Its success in these settings is attributed to the ability of engrafting immune cells to eliminate cancer cells or deplete the HIV reservoir (graft-versus-host effect [GvHE]). However, alloHSCT is commonly associated with graft-versus-host diseases (GvHDs) causing significant morbidity and mortality, thereby requiring development of novel allogeneic HSCT protocols and therapies promoting GvHE without GvHD using physiologically relevant preclinical models. Here we evaluated the outcomes of major histocompatibility complex-matched T-cell receptor α/β-depleted alloHSCT in Mauritian cynomolgus macaques (MCMs). Following T-cell receptor α/β depletion, bone marrow cells were transplanted into major histocompatibility complex-identical MCMs conditioned with total body irradiation. GvHD prophylaxis included sirolimus alone in two animals or tacrolimus with cyclophosphamide in another two animals. Posttransplant chimerism was determined by sequencing diagnostic single-nucleotide polymorphisms to quantify the amounts of donor and recipient cells present in blood. Animals treated posttransplant with sirolimus developed nearly complete chimerism with acute GvHD. In the cyclophosphamide and tacrolimus treatment group, animals developed mixed chimerism without GvHD, with long-term engraftment observed in one animal. None of the animals developed cytomegalovirus infection. These studies indicate the feasibility of alloHSCT engraftment without GvHD in an MHC-identical MCM model following complete myeloablative conditioning and anti-GvHD prophylaxis with posttransplant cyclophosphamide and tacrolimus. Further exploration of this model will provide a platform for elucidating the mechanisms of GvHD and GvHE and for testing novel alloHSCT modalities for HIV infection.