Immunotherapy of established tumors in mice by intratumoral injection of interleukin-2 plasmid DNA: induction of CD8+ T-cell immunity

• Published in: Cancer gene therapy Vol. 5; no. 5; p. 321
• Main Authors: Saffran, D C, Horton, H M, Yankauckas, M A, Anderson, D, Barnhart, K M, Abai, A M, Hobart, P, Manthorpe, M, Norman, J A, Parker, S E
• Format: Journal Article
• Language: English
• Published: England 01-09-1998
• Subjects: Animals; Carcinogenicity Tests; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - therapy; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Dose-Response Relationship, Drug; Drug Carriers - pharmacology; Immunotherapy - methods; Injections, Intralesional; Interleukin-2 - genetics; Interleukin-2 - pharmacology; Kidney Neoplasms - immunology; Kidney Neoplasms - therapy; Lipids - chemistry; Lipids - pharmacology; Mice; Mice, Inbred BALB C; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy; Phosphatidylethanolamines - chemistry; Phosphatidylethanolamines - pharmacology; Plasmids - genetics; Plasmids - pharmacology; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - pharmacology
• ISSN: 0929-1903

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.