Antitumor properties of influenza virus vectors

We are investigating the potential use of influenza virus vectors expressing selected tumor-associated antigens (TAAs) as therapeutic agents in anticancer strategies. Previously, we have shown that recombinant influenza viruses expressing a model TAA mediated the regression of established pulmonary metastases in mice through the induction of cytotoxic T-cell responses (N. P. Restifo et al., Virology, 249: 89-97, 1998). We have now expanded these observations in the mouse model using survival as the end point of the assay. Animals with a high tumor burden showed extended survival times when treated with a recombinant influenza virus expressing a TAA, but they finally succumbed to death. Death was associated with the presence of a small number of large tumors in lungs. Interestingly, these tumors were found to express undetectable levels of the TAAs because of a down-regulation in the TAA-specific mRNA levels. On the other hand, mice with five times lower tumor burden showed complete tumor regression and survival for6 six months when treated with the recombinant virus. These animals showed protection against a tumor challenge 6 months after treatment. Our results suggest that recombinant influenza viruses may be useful as therapeutic agents for the prevention and treatment of cancers with known TAAs.