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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-02-0503.
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Blood, 1 December 2002, Vol. 100, No. 12, pp. 4146-4153
NEOPLASIA
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
From the Calgary Laboratory Services, AB,
Canada; the Cancer Biology Research Group, the Department
of Pathology, the Department of Microbiology and Infectious Diseases,
and the Department of Medical Biochemistry, University of Calgary, AB,
Canada; and the Department of Medicine, University of
Alberta, and the Canadian Blood Services, Edmonton, AB,
Canada.
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 the
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 lymphoma cell lines Raji and CA46 but not Daudi,
Ramos, or ST486. Moreover, when Raji and Daudi cell lines were
grown subcutaneously in severe combined immunodeficient/nonobese diabetic (SCID/NOD) mice and subsequently injected with
reovirus intratumorally or intravenously, significant regression was
observed in the Raji-induced, 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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