Antitumor properties of influenza virus vectors

We are investigating the potential use of influenza virus vectors expressin g selected tumor-associated antigens (TAAs) as therapeutic agents in antica ncer strategies. Previously, we have shown that recombinant influenza virus es 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 o bservations in the mouse model using survival as,the end point of the assay . Animals with a high tumor burden showed extended survival times when trea ted with a recombinant influenza virus expressing a TAA, but they finally s uccumbed to death. Death was associated with the presence of a small number of large tumors in lungs. Interestingly, these tumors were found to expres s undetectable levels of the TAAs because of a down-regulation in the TAA-s pecific mRNA levels. On the other hand, mice with five times lower tumor bu rden shelved 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 recom binant influenza viruses may be useful as therapeutic agents for the preven tion and treatment of cancers with known TAAs.