Antitumor effect of interleukin-2 entrapped in liposomes on murine renal cell carcinoma.
Antitumor effects of interleukin-2 entrapped in liposomes (IL-2 liposomes) on Renca, murine renal cell carcinoma of spontaneous origin, were evaluated by in vivo and in vitro experiments. As a local treatment model, IL-2 liposomes at a dose of 1.0 x 10(4) units were for 7 days injected adjacent to the Renca tumors inoculated in the back of BALB/c mice. The treatment inhibited the tumor growth and prolonged the survival time of mice significantly compared to the control (p < 0.01). Serum IL-2 levels after subcutaneous administration of IL-2 liposomes confirmed its slow releasing mechanism into blood circulation. The spleen cells from mice following the IL-2 liposome treatment showed higher cytotoxicity in vitro than that of IL-2 alone using Renca, YAC-1, and P-815 cells, which was determined by 51Cr-release assay. Indirect immunoperoxidase staining of tumor-infiltrating lymphocytes (TILs) showed that accumulation of Lyt-2+ and L3T4+ cells were seen in the tumor treated with IL-2 liposomes. These results indicate that IL-2 liposomes have a long-acting cytotoxicity against renal cell carcinoma caused by a slow release mechanism generated through the efficient local immune response mediated by TILs.
Oya
M
M
Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008081:Liposomes; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013154:Spleen / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes