Oncolytic vesicular stomatitis virus expressing interferon-γ has enhanced therapeutic activity.
Oncolytic viruses are known to stimulate the antitumor immune response by specifically replicating in tumor cells. This is believed to be an important aspect of the durable responses observed in some patients and the field is rapidly moving toward immunotherapy. As a further means to engage the immune system, we engineered a virus, vesicular stomatitis virus (VSV), to encode the proinflammatory cytokine interferon-γ. We used the 4T1 mammary adenocarcinoma as well as other murine tumor models to characterize immune responses in tumor-bearing animals generated by treatment with our viruses. The interferon-γ-encoding virus demonstrated greater activation of dendritic cells and drove a more profound secretion of proinflammatory cytokines compared to the parental virus. From a therapeutic point of view, the interferon-γ virus slowed tumor growth, minimized lung tumors, and prolonged survival in several murine tumor models. The improved efficacy was lost in immunocompromized animals; hence the mechanism appears to be T-cell-mediated. Taken together, these results demonstrate the ability of oncolytic viruses to act as immune stimulators to drive antitumor immunity as well as their potential for targeted gene therapy.
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, Canada; University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Ontario, Canada.
Marie-Claude
MC
Bourgeois-Daigneault
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, Canada; University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Ontario, Canada.
Dominic Guy
DG
Roy
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research , Ottawa, Ontario, Canada.
Theresa
T
Falls
Deeley Research Centre, British Columbia Cancer Agency , Victoria, British Columbia, Canada.
Kwame
K
Twumasi-Boateng
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research , Ottawa, Ontario, Canada.
Lauren Elizabeth
LE
St-Germain
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, Canada; University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Ontario, Canada.
Monique
M
Marguerie
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, Canada; University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Ontario, Canada.
Vanessa
V
Garcia
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, Canada; University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Ontario, Canada.
Mohammed
M
Selman
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research , Ottawa, Ontario, Canada.
Victoria Ann
VA
Jennings
Deeley Research Centre, British Columbia Cancer Agency , Victoria, British Columbia, Canada.
Jessica
J
Pettigrew
Deeley Research Centre, British Columbia Cancer Agency , Victoria, British Columbia, Canada.
Sally
S
Amos
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research , Ottawa, Ontario, Canada.
Jean-Simon
JS
Diallo
Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Brad
B
Nelson
Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, Canada; University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Ontario, Canada.
John Cameron
JC
Bell