Pharmacokinetics and antitumor effects of an interleukin-2 immunocomplexing agent in murine renal cell carcinoma.
BACKGROUND
Conventional therapy for renal cell carcinoma (RCC) using systemic administration of interleukin-2 (IL-2) has shown limited anti-tumor action. The purpose of this study was to investigate the anti-tumor effects of a newly developed immune complex of IL-2 (IC) against RCC.


METHODS
IC was prepared by mixing IL-2 and an anti-IL-2 monoclonal antibody at a molar ratio of 2:1. The pharmacokinetics and anti-tumor effects of IC were then studied in a murine RCC line, Renca.


RESULTS
Serum IL-2 levels were sustained longer in mice given IC than in mice given IL-2 alone after either subcutaneous or intratumoral injections. After an intratumoral injection of IC, the IL-2 concentration in the tumor nodules remained higher compared with mice given IL-2 alone. The anti-tumor effect was most pronounced in mice treated with intratumoral injections of IC.


CONCLUSIONS
Results obtained here indicate that an immune complex of IL-2 provides a useful tool for the treatment of RCC by altering the pharmacokinetics of IL-2 in vivo.
Oya
M
M
Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
Marumo
K
K
Murai
M
M
Tazaki
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D018796:Immunoconjugates / Q000008:administration & dosage / Q000627:therapeutic use*; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007376:Interleukin-2; D011994:Recombinant Proteins