Tumor vaccines: effects and fate of IL-2 transfected murine melanoma cells in vivo.
We have previously demonstrated the general usefulness of the adenovirus-enhanced transferrinfection (AVET) in the generation of IL-2 producing tumor vaccines. By optimizing different parameters of the transfection protocol we were able to transform the poorly immunogenic M-3 mouse melanoma cell line into a potent immunogen. A long-lasting immunity was demonstrated after administration of the IL-2 releasing vaccine, since immunized animals successfully rejected native M-3 melanoma cells even after a period of more than 6 months. We also demonstrated that in vivo administration of such a vaccine is safe since transmission of the transfected IL-2 gene in host organs was not detected. IL-2 production ceased 2 days after injection because the engineered cells were destroyed. However, RT-PCR analysis of the site of vaccine injection suggests that IL-2 exerts its effects not only directly but also by inducing a set of other immunomodulator cytokines in situ that are probably indispensable in inducing a host response. We conclude that AVET of IL-2 into tumor cells is a safe and efficient method for the generation of tumor vaccines.
Maass
G
G
Research Institute of Molecular Pathology, Vienna, Austria.
Schweighoffer
T
T
Berger
M
M
Schmidt
W
W
Herbst
E
E
Zatloukal
K
K
Buschle
M
M
Birnstiel
M L
ML
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000494:pharmacology
D007376:Interleukin-2; D014613:Vaccines, Attenuated