Pharmacokinetics and antitumor effects of an interleukin-2 immunocomplexing agent in murine renal cell carcinoma

Int J Urol. 1996 Mar;3(2):141-4. doi: 10.1111/j.1442-2042.1996.tb00499.x.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / immunology
  • Cytotoxicity, Immunologic / drug effects
  • Female
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / therapeutic use*
  • Injections, Intralesional
  • Injections, Subcutaneous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacokinetics
  • Interleukin-2 / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / immunology
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Immunoconjugates
  • Interleukin-2
  • Recombinant Proteins