title: Application of cytokine drug delivery systems to the immunotherapy of renal cell carcinoma in mice.
abstract: We have investigated the antitumor effects of human lymphoblastoid interferon (HLBI) mini-pellets, interleukin-2 (IL-2) entrapped in liposome (IL-2 liposome) and an immune complex of IL-2 and monoclonal antibody against IL-2 (IC-1). The HLBI mini-pellets were administered to nude mice bearing a human renal cancer cell line (KU-2). HLBI levels remained detectable both in the tumor tissue and the serum up to 10 days after peritumor injection. The HLBI mini-pellet significantly suppressed tumor growth by peritumor administration. The antitumor effect of IL-2 liposome on Renca, a murine renal cancer, resulted in the inhibition of tumor growth. An accumulation of Lyt-2(-) and L3T4 lymphocytes was seen in the tumor tissue which was treated with IL-2 liposomes. The IC-1 was prepared by mixing IL-2 and anti-IL-2 monoclonal antibody at a molar ratio of 2: 1. Plasma IL-2 levels were sustained longer in mice given the IC-1 than in mice given IL-2 alone. The IC-1 complex exerted a more significant antitumor effect by local administration in Renca-bearing mice than the administration of IL-2 alone. We speculated that these effects were a result of sustained tumor IL-2 levels due to the increase in molecular weight. The results we obtained indicate that the cytokine drug delivery system has a long-acting cytotoxicity by administration to the tumor sites through efficient stimulation of the local immune response, and thus provides a useful tool for treatment of renal cell carcinoma.
authors.affiliation: Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Marumo
authors.forename: M
authors.initials: M
authors.lastname: Oya
authors.forename: M
authors.initials: M
authors.lastname: Murai
authors.forename: H
authors.initials: H
authors.lastname: Tazaki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000276:immunology / Q000493:pharmacokinetics*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000970:Antineoplastic Agents; C508594:IL2 protein, human; D007376:Interleukin-2; D008081:Liposomes
keywords: drug delivery system; interferon; interleukin-2; renal cell carcinoma