Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft model

Nat Med. 1999 Jul;5(7):817-22. doi: 10.1038/10541.

Abstract

The elusive and enigmatic origin of AIDS-associated Kaposi's sarcoma (AIDS-KS) makes it a complex tumor and therefore difficult to treat. Here we demonstrate that AIDS-KS cells express surface interleukin-4 (IL-4) receptors, and that IL-4 toxin (IL-4(38-37)-PE38KDEL) is specifically cytotoxic to these cells. Intratumoral, intraperitoneal and intravenous administration of IL-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable anti-tumor activity in a dose-dependent manner, with highest dose producing durable complete responses. Metabolic changes, including cachexia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin treatment. This report establishes IL-4(38-37)-PE38KDEL as an experimental therapeutic agent for the treatment of AIDS-KS.

MeSH terms

  • ADP Ribose Transferases*
  • Acquired Immunodeficiency Syndrome / complications*
  • Animals
  • Bacterial Toxins*
  • Cachexia / prevention & control
  • Exotoxins / therapeutic use*
  • Humans
  • Immunotoxins / therapeutic use*
  • Interleukin-4 / therapeutic use*
  • Lymphopenia / prevention & control
  • Mice
  • Mice, Nude
  • Peptide Fragments / therapeutic use
  • Receptors, Interleukin-4 / drug effects
  • Receptors, Interleukin-4 / physiology*
  • Recombinant Fusion Proteins / therapeutic use
  • Sarcoma, Kaposi / drug therapy*
  • Sarcoma, Kaposi / etiology
  • Sarcoma, Kaposi / immunology
  • Sarcoma, Kaposi / physiopathology
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Virulence Factors*

Substances

  • Bacterial Toxins
  • Exotoxins
  • Immunotoxins
  • Peptide Fragments
  • Receptors, Interleukin-4
  • Recombinant Fusion Proteins
  • Virulence Factors
  • interleukin 4 (38-37)-PE38KDEL
  • Interleukin-4
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa