Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2

Biotherapy. 1993;6(3):225-31. doi: 10.1007/BF01878084.

Abstract

We have investigated biological properties of an immune complex of recombinant interleukin-2 (rIL-2) and a monoclonal antibody against rIL-2 in mice for induction of killer cells and for anti-tumor activity. We have also examined the clearance of subcutaneously-injected immune complex in mice and compared it with that of rIL-2 alone. Plasma rIL-2 levels were sustained longer in mice given the immune complex than in mice given rIL-2 alone at a dose of 10 micrograms/mouse, and they were detectable even at 24 hours after the administration of the immune complex, while they fell to undetectable levels by 6 hours after the administration of rIL-2 alone. A more significant portion of rIL-2 was detected in lymph nodes after subcutaneous injection of the immune complex than that of rIL-2 alone. Splenic lymphocytes from mice given the immune complex demonstrated a higher killer cell activity against YAC-1 cells than those from mice given rIL-2 alone. The immune complex also exerted more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than rIL-2 alone. Our results indicate that immunocomplexing of rIL-2 with an antibody against rIL-2 provides a useful tool as the drug delivery system for cancer therapy using rIL-2.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antigen-Antibody Complex / immunology*
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Female
  • Immunotoxins / pharmacology
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacokinetics
  • Interleukin-2 / pharmacology*
  • Mice
  • Recombinant Proteins
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Antineoplastic Agents
  • Immunotoxins
  • Interleukin-2
  • Recombinant Proteins