title: Immunotherapy of established tumors in mice by intratumoral injection of interleukin-2 plasmid DNA: induction of CD8+ T-cell immunity.
abstract: Intratumoral (i.t.) injection of a plasmid DNA vector encoding the murine interleukin-2 (IL-2) gene was used to treat established renal cell carcinoma (Renca) tumors in BALB/c mice. Tumor regression was observed in 60-90% of mice that were injected i.t. for 4 days with IL-2 plasmid DNA complexed with the cationic lipid DMRIE/DOPE ((+/-)-N-(2-hydroxyethyl)-N,N-dimethyl-2,3-bis(tetradecyloxy)-1-propa naminium bromide/dioleoylphosphatidylethanolamine). The mice remained tumor-free until the conclusion of the study, which was 4 months after tumor challenge. In a rechallenge experiment, mice that were rendered tumor-free for 6 months by IL-2 plasmid DNA treatment rejected a subsequent challenge of Renca cells but could not reject a challenge with the unrelated, syngeneic CT-26 tumor. Spleen cells from cured mice contained Renca-specific cytotoxic T lymphocytes, and adoptive transfer of mixed lymphocyte cultures into naive mice at 2 days after challenge with Renca cells prevented tumor growth. In vivo depletion of T-cell subsets at the time of i.t. injection with IL-2 plasmid DNA demonstrated that CD8+ T cells, but not CD4+ T cells, were the primary effectors of the antitumor response.
authors.affiliation: Vical Inc., San Diego, California 92121, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Saffran
authors.forename: H M
authors.initials: HM
authors.lastname: Horton
authors.forename: M A
authors.initials: MA
authors.lastname: Yankauckas
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.forename: K M
authors.initials: KM
authors.lastname: Barnhart
authors.forename: A M
authors.initials: AM
authors.lastname: Abai
authors.forename: P
authors.initials: P
authors.lastname: Hobart
authors.forename: M
authors.initials: M
authors.lastname: Manthorpe
authors.forename: J A
authors.initials: JA
authors.lastname: Norman
authors.forename: S E
authors.initials: SE
authors.lastname: Parker
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015197:Carcinogenicity Tests; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods*; D015552:Injections, Intralesional; D007376:Interleukin-2 / Q000235:genetics* / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D007376:Interleukin-2; D008055:Lipids; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; C094877:dioleoyl phosphatidylethanolamine