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 for >6 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.