title: Reovirus as a successful ex vivo purging modality for multiple myeloma.
abstract: Autologous stem cell rescue (ASCT) following high-dose myeloablative chemotherapy is considered to be a therapeutic option for many multiple myeloma (MM) patients; however relapse post ASCT presents a major challenge. The oncolytic potential of reovirus has been previously demonstrated and is currently undergoing phase I monotherapy clinical trials for MM and phase II/III clinical trials for solid tumors. Here we tested the hypothesis that reovirus can successfully purge MM in a murine model that partially recapitulates human MM. RPMI 8226, MM1S, H929 and U266 human myeloma cell lines were exposed to reovirus and oncolysis was assessed. Apheresis product admixed with MM cells was purged with live reovirus (LV) or dead virus (DV) and purging efficacy was monitored via flow cytometry, reverse transcribed-PCR (RT-PCR) and disease relapse in non obese diabetic/severe combined immune deficient (NOD/SCID) mice. Significant LV purging was seen with MM1S, H929 and U266 and the complete ex vivo purging achieved with RPMI 8226 was confirmed by flow cytometry, RT-PCR and absence of disease relapse in vivo. Mice that received LV-purged autografts exhibited 100% survival in comparison to mice that received DV-purged controls. Reovirus's unique ability to kill MM while sparing hematopoietic stem cells places it as an attractive purging agent for MM during ASCT.
authors: 1] Department of Oncology, University of Calgary, Calgary, Alberta, Canada [2] Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: C M
authors: CM
authors: Thirukkumaran
authors: Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: Z Q
authors: ZQ
authors: Shi
authors: Calgary Laboratory Services, Calgary, Alberta, Canada.
authors: J
authors: J
authors: Luider
authors: 1] Department of Oncology, University of Calgary, Calgary, Alberta, Canada [2] Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: K
authors: K
authors: Kopciuk
authors: 1] Department of Oncology, University of Calgary, Calgary, Alberta, Canada [2] Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: N
authors: N
authors: Bahlis
authors: 1] Department of Oncology, University of Calgary, Calgary, Alberta, Canada [2] Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: P
authors: P
authors: Neri
authors: Department of Public Health Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors: M
authors: M
authors: Pho
authors: 1] Department of Oncology, University of Calgary, Calgary, Alberta, Canada [2] Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: D
authors: D
authors: Stewart
authors: Calgary Laboratory Services, Calgary, Alberta, Canada.
authors: A
authors: A
authors: Mansoor
authors: 1] Department of Oncology, University of Calgary, Calgary, Alberta, Canada [2] Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors: D G
authors: DG
authors: Morris
mesh_terms: D000818:Animals; D001781:Blood Component Removal; D016465:Bone Marrow Purging / Q000379:methods*; D002460:Cell Line; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000628:therapy*; D050130:Oncolytic Virotherapy; D012008:Recurrence; D012087:Reoviridae; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D049452:Green Fluorescent Proteins
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