title: Selective purging of human multiple myeloma cells from autologous stem cell transplantation grafts using oncolytic myxoma virus.
abstract: Autologous stem cell transplantation and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after autologous stem cell transplantation. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellular apoptosis while fully sparing normal hematopoietic stem and progenitor cells. The specificity of this elimination is based on strong binding of the virus to myeloma cells coupled with an inability of the virus to bind or infect CD34(+) hematopoietic stem and progenitor cells. These 2 features allow myxoma to readily identify and distinguish even low levels of myeloma cells in complex mixtures. This ex vivo rabbit-specific oncolytic poxvirus called myxoma virus treatment also effectively inhibits systemic in vivo engraftment of human myeloma cells into immunodeficient mice and results in efficient elimination of primary CD138(+) myeloma cells contaminating patient hematopoietic cell products. We conclude that ex vivo myxoma treatment represents a safe and effective method to selectively eliminate myeloma cells from hematopoietic autografts before reinfusion.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, Florida, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bartee
authors.forename: Winnie M
authors.initials: WM
authors.lastname: Chan
authors.forename: Jan S
authors.initials: JS
authors.lastname: Moreb
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009233:Myxoma virus / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D050504:Oncolytic Viruses / Q000276:immunology*; D011817:Rabbits; D055502:Secondary Prevention; D053668:Syndecan-1 / Q000276:immunology / Q000378:metabolism; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D053668:Syndecan-1; D049452:Green Fluorescent Proteins