Virotherapy using myxoma virus prevents lethal graft-versus-host disease following xeno-transplantation with primary human hematopoietic stem cells.
Graft-versus-host disease (GVHD) is a potentially lethal clinical complication arising from the transfer of alloreactive T lymphocytes into immunocompromised recipients. Despite conventional methods of T cell depletion, GVHD remains a major challenge in allogeneic hematopoietic cell transplant. Here, we demonstrate a novel method of preventing GVHD by ex vivo treatment of primary human hematopoietic cell sources with myxoma virus, a rabbit specific poxvirus currently under development for oncolytic virotherapy. This pretreatment dramatically increases post-transplant survival of immunocompromised mice injected with primary human bone marrow or peripheral blood cells and prevents the expansion of human CD3(+) lymphocytes in major recipient organs. Similar viral treatment also prevents human-human mixed alloreactive T lymphocyte reactions in vitro. Our data suggest that ex vivo virotherapy with myxoma virus can be a simple and effective method for preventing GVHD following infusion of hematopoietic products containing alloreactive T lymphocytes such as: allogeneic hematopoietic stem and progenitor cells, donor leukocyte infusions and blood transfusions.
Department of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, Florida, United States of America.
Eric
E
Bartee
Amy
A
Meacham
Elizabeth
E
Wise
Christopher R
CR
Cogle
Grant
G
McFadden
D000818:Animals; D001803:Blood Transfusion; D001854:Bone Marrow Cells / Q000166:cytology; D017252:CD3 Complex / Q000096:biosynthesis; D002469:Cell Separation; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009233:Myxoma virus / Q000378:metabolism*; D011213:Poxviridae Infections / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000821:virology; D014183:Transplantation, Heterologous; D014777:Virus Diseases / Q000378:metabolism
D017252:CD3 Complex