Transfectant influenza A viruses are effective recombinant immunogens in the treatment of experimental cancer.
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.
Restifo
N P
NP
Laboratories of the Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland, 20892, USA.
Surman
D R
DR
Zheng
H
H
Palese
P
P
Rosenberg
S A
SA
García-Sastre
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology*; D012313:RNA / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; C039919:RNA, recombinant; D012313:RNA