Reovirus as a successful ex vivo purging modality for multiple myeloma

• Published in: Bone marrow transplantation (Basingstoke) Vol. 49; no. 1; pp. 80 - 86
• Main Authors: Thirukkumaran, C M, Shi, Z Q, Luider, J, Kopciuk, K, Bahlis, N, Neri, P, Pho, M, Stewart, D, Mansoor, A, Morris, D G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2014; Nature Publishing Group
• Subjects: 631/250/1854/2813; 692/699/67/1990/804; 692/700/565/1331; 692/700/565/545/576; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blood Component Removal; Bone marrow; Bone Marrow Purging - methods; Bone marrow, stem cells transplantation. Graft versus host reaction; Cancer; Care and treatment; Cell Biology; Cell Line; Cell Line, Tumor; Flow Cytometry; Green Fluorescent Proteins - chemistry; Hematologic and hematopoietic diseases; Hematology; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Internal Medicine; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred NOD; Mice, SCID; Multiple myeloma; Multiple Myeloma - therapy; Oncology, Experimental; Oncolytic Virotherapy; original-article; Public Health; Recurrence; Relapse; Reoviridae; Reovirus; Reoviruses; Reverse Transcriptase Polymerase Chain Reaction; Stem cell transplantation; Stem Cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Treatment Outcome; multiple myeloma; murine model; reovirus; transplantation; purging; Immunopathology; Animal model; Hematology; Rodentia; Malignant hemopathy; Transplantation; Myeloma; in vivo murine model; In vivo; Vertebrata; Mammalia; Treatment; Immunoglobulinopathy; Ex vivo; Mouse; Surgery; Lymphoproliferative syndrome; Graft; Cancer
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2013.130

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.