title: Genetic modification of cells by receptor-mediated adenovirus-augmented gene delivery: a new approach for immunotherapy of cancer.
abstract: 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.
authors.affiliation: Research Institute of Molecular Pathology (I.M.P.), Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Zatloukal
authors.forename: A
authors.initials: A
authors.lastname: Schneeberger
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: F
authors.initials: F
authors.lastname: Koszik
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
authors.forename: E
authors.initials: E
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Cotten
authors.forename: M
authors.initials: M
authors.lastname: Buschle
authors.forename: G
authors.initials: G
authors.lastname: Maass
authors.forename: G
authors.initials: G
authors.lastname: Stingl
mesh_terms: 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*
chemical_list: D007376:Interleukin-2; D014612:Vaccines