TRANSFECTANT INFLUENZA-A VIRUSES ARE EFFECTIVE RECOMBINANT IMMUNOGENSIN THE TREATMENT OF EXPERIMENTAL CANCER

Using reverse genetics methods, we constructed three different transfe ctant influenza A viruses encoding an Ld-restricted, nine amino-acid-l ong fragment, corresponding to amino-acid residues 876-884, of beta-ga lactosidase (beta-gal). Sequences encoding this epitope were nested wi thin the hemagglutinin (HA) or neuraminidase (NA) open reading frames. Alternatively, an independent beta-gal mini-gene, preceded by an endo plasmic reticulum insertion signal sequence, was placed in a bicistron ic arrangement in the NA RNA segment of the virus. All three transfect ants mediated the presentation of the epitope to a beta-gal-specific C TL clone. Furthermore, each of the three transfectant viruses expressi ng the beta-gal fragment elicited specific cytolytic responses in vivo . Most importantly, these H1N1 transfectants mediated the regression o f established murine pulmonary metastases. Tumor regression in mice wa s also achieved in the presence of preexisting immunity against an H3N 2 influenza A virus serotype. Nononcogenic and nonintegrating, transfe ctant influenza A viruses are attractive candidates for development as antitumor vaccines. (C) 1998 Academic Press.