Interleukin-4 receptors expressed on tumor cells may serve as a target for anticancer therapy using chimeric Pseudomonas exotoxin

Int J Cancer. 1994 Sep 1;58(5):744-8. doi: 10.1002/ijc.2910580520.

Abstract

Interleukin-4 receptors (IL4R) are present on a wide variety of human cancer cells derived from both hematopoietic and epithelial malignancies. We have targeted IL4R on a human solid tumor xenograft with chimeric proteins composed of human IL4 (hIL4) and 2 different mutant forms of a powerful bacterial toxin, Pseudomonas exotoxin A (PE). The 2 chimeric toxins, termed hIL4-PE4E and hIL4-PE38QQR, showed specific, hIL4R-dependent and dose-dependent antitumor activities. Neither of the chimeric toxins showed antitumor potency when the ADP-ribosylation activity of the toxin was inactivated by mutagenesis. One of the chimeras, hIL4-PE38QQR, caused a complete although transient regression of established solid tumors. These observations indicate that hIL4-PE chimeric proteins should be further evaluated for the treatment of human malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases*
  • Animals
  • Bacterial Toxins*
  • Carcinoma, Squamous Cell / drug therapy*
  • Exotoxins / administration & dosage*
  • Exotoxins / chemistry
  • Exotoxins / toxicity
  • Humans
  • Interleukin-4 / chemistry
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Receptors, Interleukin-4
  • Receptors, Mitogen / metabolism*
  • Recombinant Fusion Proteins
  • Transplantation, Heterologous
  • Virulence Factors*

Substances

  • Bacterial Toxins
  • Exotoxins
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Recombinant Fusion Proteins
  • Virulence Factors
  • Interleukin-4
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa