Genetic modification of cells by receptor-mediated adenovirus-augmented gene delivery: a new approach for immunotherapy of cancer.
Most concepts of gene therapy of cancer are based on the generation of an enhanced immune response against the cancer by means of vaccination with gene-modified cancer cells. We have investigated the applicability of a new gene transfer technique which uses the receptor-mediated endocytosis pathway and the endosome disruption activity of adenovirus for the generation of a cancer vaccine consisting of interleukin-2 (IL-2)-transfected, irradiated murine melanoma cells (clone M-3). This technique resulted in very high IL-2 expression (in the range of 30,000 Units IL-2/10(6) cells/24 hrs) in the transfected cells without the need to selection of stably expressing cell clones. We found that this high IL-2 expression of the melanoma cells correlates with high efficacy of the vaccine. Immunization of animals with this vaccine elicits a systemic T-cell-mediated immune response which protects from tumor development after implantation of highly tumorigenic doses of wild-type melanoma cells.
Zatloukal
K
K
Research Institute of Molecular Pathology (I.M.P.), Vienna, Austria.
Schneeberger
A
A
Berger
M
M
Koszik
F
F
Schmidt
W
W
Wagner
E
E
Cotten
M
M
Buschle
M
M
Maass
G
G
Stingl
G
G
D000256:Adenoviridae; D000818:Animals; D018014:Gene Transfer Techniques; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D007376:Interleukin-2 / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D014162:Transfection; D014612:Vaccines / Q000008:administration & dosage*
D007376:Interleukin-2; D014612:Vaccines