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Autografting

Reovirus as a successful ex vivo purging modality for multiple myeloma

Bone Marrow Transplantation volume 49, pages 80–86 (2014)Cite this article

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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.

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Acknowledgements

We thank the Southern Alberta Bone Marrow Transplant Unit and the Apheresis Unit/Blood Bank of the Foothills Medical Centre for their support of this study.

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Authors and Affiliations

  1. Department of Oncology, University of Calgary, Calgary, Alberta, Canada

    C M Thirukkumaran, K Kopciuk, N Bahlis, P Neri, D Stewart & D G Morris

  2. Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada

    C M Thirukkumaran, Z Q Shi, K Kopciuk, N Bahlis, P Neri, D Stewart & D G Morris

  3. Calgary Laboratory Services, Calgary, Alberta, Canada

    J Luider & A Mansoor

  4. Department of Public Health Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    M Pho

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  1. C M Thirukkumaran
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  2. Z Q Shi
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  5. N Bahlis
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  8. D Stewart
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  10. D G Morris
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Correspondence to D G Morris.

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Thirukkumaran, C., Shi, Z., Luider, J. et al. Reovirus as a successful ex vivo purging modality for multiple myeloma. Bone Marrow Transplant 49, 80–86 (2014). https://doi.org/10.1038/bmt.2013.130

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