IMMUNOTHERAPY OF ESTABLISHED TUMORS IN MICE BY INTRATUMORAL INJECTIONOF INTERLEUKIN-2 PLASMID DNA - INDUCTION OF CD8(-CELL IMMUNITY() T)

Intratumoral (i.t.) injection of a plasmid DNA vector encoding the mur ine interleukin-2 (IL-2) gene was used to treat established renal cell carcinoma (Renca) tumors in BALB/c mice. Tumor regression was observe d in 60-90% of mice that were injected i.t. for 4 days with IL-2 plasm id DNA complexed with the cationic lipid DMRIE/DOPE ,N-dimethyl-2,3-bi s(tetradecyloxy)-1-propanaminium bromide/dioleoylphosphatidylethanolam ine The mice remained tumor-free until the conclusion of the study, wh ich was 4 months after tumor challenge. In a rechallenge experiment, m ice that were rendered tumor-free for 6 months by IL-2 plasmid DNA tre atment rejected a subsequent challenge of Renca cells but could not re ject a challenge with the unrelated, syngeneic CT-26 tumor. Spleen cel ls from cured mice contained Renca-specific cytotoxic T lymphocytes, a nd 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 p lasmid DNA demonstrated that CD8(+) T cells, but not CD4(+) T cells, w ere the primary effecters of the antitumor response.