Reovirus therapy of lymphoid malignancies.
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.
Alain
Tommy
T
Calgary Laboratory Services, AB, Canada.
Hirasawa
Kensuke
K
Pon
Kelly J
KJ
Nishikawa
Sandra G
SG
Urbanski
Stefan J
SJ
Auer
Yvonna
Y
Luider
Joanne
J
Martin
Anita
A
Johnston
Randal N
RN
Janowska-Wieczorek
Anna
A
Lee
Patrick W K
PW
Kossakowska
Anna E
AE
D000818:Animals; D000914:Antibodies, Viral / Q000627:therapeutic use*; D016923:Cell Death; D002999:Clone Cells / Q000821:virology; D006412:Hematopoietic Stem Cells / Q000821:virology; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012089:Mammalian orthoreovirus 3 / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D012088:Reoviridae Infections; D014407:Tumor Cells, Cultured
D000914:Antibodies, Viral