Abstract:
:Using reverse genetics methods, we constructed three different transfectant influenza A viruses encoding an Ld-restricted, nine amino-acid-long fragment, corresponding to amino-acid residues 876-884, of beta-galactosidase (beta-gal). Sequences encoding this epitope were nested within the hemagglutinin (HA) or neuraminidase (NA) open reading frames. Alternatively, an independent beta-gal mini-gene, preceded by an endoplasmic reticulum insertion signal sequence, was placed in a bicistronic arrangement in the NA RNA segment of the virus. All three transfectants mediated the presentation of the epitope to a beta-gal-specific CTL clone. Furthermore, each of the three transfectant viruses expressing the beta-gal fragment elicited specific cytolytic responses in vivo. Most importantly, these H1N1 transfectants mediated the regression of established murine pulmonary metastases. Tumor regression in mice was also achieved in the presence of preexisting immunity against an H3N2 influenza A virus serotype. Nononcogenic and nonintegrating, transfectant influenza A viruses are attractive candidates for development as antitumor vaccines.
journal_name
Virologyjournal_title
Virologyauthors
Restifo NP,Surman DR,Zheng H,Palese P,Rosenberg SA,García-Sastre Adoi
10.1006/viro.1998.9330subject
Has Abstractpub_date
1998-09-15 00:00:00pages
89-97issue
1eissn
0042-6822issn
1096-0341pii
S0042682298993308journal_volume
249pub_type
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