Inhibition of Daudi tumor formation by inactive influenza virus in a nude mouse model

In this work, our in vitro model of viral oncolysis (Daudi lymphoma cells and A/X47 heat-inactivated influenza virus = X56) was adapted to in vivo conditions in nude ICR mice. The tumorigenicity of Daudi cells in nude mice was inhibited following preincubation with X56 virus, when virus and cells were injected simultaneously, or when X56 virus was injected 10 days after the cells. Established tumors regressed when X56 was injected into the tumors. The participation of the immune system in the mechanism of action of the virus was determined by comparing the immunological response to X56 virus and to Daudi-X56 cells in nude and normal ICR mice. Only the normal mice produced influenza hemagglutination inhibition antibodies and cytotoxic antibodies directed against Daudi cells when challenged by either the X56 virus or Daudi X56 cells. In nude mice, natural killer cells did not respond against Daudi-X56 cells, and interferon production was too low to be involved in the process. Thus, the mode of action of X56 in vivo appears to be due to the direct toxic effect of the virus on the Daudi cells. Since the X56 virus was avirulent in normal mice, it may be a potent and safe oncolytic agent.