title: Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor.
abstract: Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in immunocompetent mice using an allogeneic mouse-mouse model. In contrast to all human MM cell lines previously tested, the murine MM cell line tested here was highly resistant to direct MYXV infection and oncolysis in vitro. Despite this in vitro resistance, we found that ex vivo MYXV-armed allogeneic bone marrow (BM) transplantation dramatically ablated pre-seeded residual MM in vivo. Unexpectedly, we show that both neutrophils and activated T cells from the donor function as virus-armed carrier cells, and MYXV-preloaded cells enhanced MM killing. Our results demonstrate a novel therapeutic paradigm for residual cancer, in which multiple classes of allotransplant leukocytes can be armed by MYXV ex vivo to enhance the graft-versus-tumor effects.
authors.affiliation: Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Cameron L
authors.initials: CL
authors.lastname: Lilly
authors.affiliation: Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Villa
authors.affiliation: Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Lemos de Matos
authors.affiliation: College of Agriculture and Life Sciences, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Haider M
authors.initials: HM
authors.lastname: Ali
authors.affiliation: Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Jess-Karan S
authors.initials: JS
authors.lastname: Dhillon
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, 1105 the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Hofland
authors.affiliation: Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Masmudur M
authors.initials: MM
authors.lastname: Rahman
authors.affiliation: DNAtrix, Inc., Houston, TX 77021, USA.
authors.forename: Winnie
authors.initials: W
authors.lastname: Chan
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, 0313 Oslo, Norway; KG Jebsen Centre for Influenza Vaccine Research, University of Oslo, 0313 Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cogle
authors.affiliation: Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
keywords: MOPC315.BM; T cells; allogenic transplant; multiple myeloma; myxoma virus; neutrophils