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.
Zheng
H
H
Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Palese
P
P
García-Sastre
A
A
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000628:therapy*; D009975:Orthomyxoviridae / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D001616:beta-Galactosidase