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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-02-0503.
Submitted February 14, 2002
Accepted July 8, 2002
Reovirus therapy of lymphoid malignancies
Tommy Alain, Kensuke Hirasawa, Kelly J Pon, Sandra G Nishikawa, Stefan J Urbanski, Yvonna Auer, Joanne Luider, Anita Martin, Randal N Johnston, Anna Janowska-Wieczorek, Patrick W K Lee, and Anna E Kossakowska*
Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Department of Pathology, University of Calgary, Calgary, AB, Canada
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Calgary Laboratory Services, Calgary, AB, Canada; Department of Pathology, University of Calgary, Calgary, AB, Canada
Calgary Laboratory Services, Calgary, AB, Canada; Department of Pathology, University of Calgary, Calgary, AB, Canada
Calgary Laboratory Services, Calgary, AB, Canada
Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Department of Medical Biochemistry, University of Calgary, Calgary, AB, Canada
Department of Medicine, University of Alberta, Edmonton, AB, Canada
Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
* Corresponding author; email: anna.kossakowska{at}cls.ab.ca.
Reoviruses infect cells that manifest an activated Ras-signaling pathway, and have been shown to effectively destroy many different types of neoplastic cells, including those derived from brain, breast, colon, ovaries, and prostate. In this study, we investigated reovirus as a potential therapeutic agent against lymphoid malignancies. A total of 9 lymphoid cell lines and 27 primary human lymphoid malignancies, as well as normal lymphocytes and hematopoietic stem/progenitor cells, were tested for susceptibility to reovirus infection. For in vitro studies, the cells were challenged with reovirus (serotype 3 Dearing), and viral infection was assessed by cytopathic effects, viability, viral protein synthesis and progeny virus production. We present evidence of efficient reovirus infection and cell lysis in the diffuse large B-cell lymphoma cell lines and Burkitt's lymphoma cell lines Raji and CA46 but not Daudi, Ramos and ST486. Moreover, when Raji and Daudi cell lines were grown subcutaneously in SCID/NOD mice and subsequently injected with reovirus intratumorally or intravenously, significant regression was observed in the Raji but not the Daudi induced tumors, which is consistent with the in vitro results. Susceptibility to reovirus infection was also detected in 21 of the 27 primary lymphoid neoplasias tested but not in the normal lymphocytes or hematopoietic stem/progenitor cells. Our results suggest that reovirus may be an effective agent against several types of human lymphoid malignancies.
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