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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-08-2508.
Submitted August 15, 2002
Accepted February 15, 2003
Reovirus oncolysis as a novel purging strategy for autologous stem cell transplantation
Chandini M Thirukkumaran, Joanne M Luider, Douglas A Stewart, Tina Cheng, Sasha M Lupichuk, Michael J Nodwell, James A Russell, Iwona A Auer, and Donald G Morris*
Department of Medicine, Tom Baker Cancer Centre, Calgary, AB, Canada
Department of Medicine and Oncology, University of Calgary, Calgary, AB, Canada
Flow Cytometry Laboratory, Calgary Laboratory Services, Calgary, AB, Canada
* Corresponding author; email: donmorri{at}cancerboard.ab.ca.
Hematological stem cell rescue after high-dose cytotoxic therapy is extensively used for the treatment of many hematopoietic and solid cancers. Gene marking studies suggest that occult tumour cells within the autograft may contribute to clinical relapse. To date purging of autografts contaminated with cancer cells has been unsuccessful. The selective oncolytic property of reovirus against a myriad of malignant histologies in in vitro, in vivo and ex vivo systems has been previously demonstrated. In the present study we have shown that reovirus can successfully purge cancer cells within autografts. Human monocytic and myeloma cell lines as well as enriched ex vivo lymphoma, myeloma and Waldenstrom macroglobulinemia patient tumour specimens were used in an experimental purging model. Viability of the cell lines or purified ex vivo tumour cells of diffuse large B-cell lymphoma, chronic lymphocytic leukemia, Waldenstrom macroglobulinemia and small lymphocytic lymphoma was significantly reduced post reovirus treatment. Further, 35S methionine labelling /SDS PAGE of cellular proteins demonstrated reovirus protein synthesis and disruption of host cell protein synthesis as early as 24hr. Admixtures of apheresis product with the above tumour cells/ cell lines treated with reovirus showed complete purging of disease. In contrast, reovirus purging of enriched ex vivo multiple myeloma, Burkitt's lymphoma and follicular lymphoma was incomplete. The oncolytic action of reovirus did not affect CD34+ stem cells or their long-term colony forming assays even after G-CSF stimulation. Our results indicate the ex vivo use of an unattenuated oncolytic virus as an attractive purging strategy for autologous stem cell transplants.
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