Targeting interleukin-4 receptors for effective pancreatic cancer therapy.

Abstract

We demonstrate that pancreatic cancer tissues express receptors for interleukin (IL)-4 in situ at high density. Using the approach of selective receptor targeting, we have tested the efficacy of a recombinant cytotoxin IL4-Pseudomonas exotoxin A, which is composed of a targeting moiety (IL-4) and a mutated form of Pseudomonas exotoxin. Our results demonstrate that this molecule exerts vigorous antitumor activity against human pancreatic tumors implanted s.c. in immunodeficient animals. Sixty percent of animals treated with intratumoral injections of IL4-Pseudomonas exotoxin A experienced complete disappearance of established tumors. Animals with pancreatic tumors implanted orthotopically exhibited prolonged survival that was significantly greater by comparison with untreated animals. Thus, IL-4 receptor-targeted cytotoxin represents a potent agent that may provide an effective therapy for pancreatic cancer.

• Authors: Koji Kawakami, Mariko Kawakami, Syed R Husain, Raj K Puri
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 13 Pg. 3575-80 (Jul 01 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12097255 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Exotoxins
• IL-4-PE40 protein, recombinant
• Receptors, Interleukin-4
• Recombinant Fusion Proteins
• Interleukin-4

Topics

• Adult
• Aged
• Animals
• Exotoxins (metabolism, pharmacology)
• Female
• Humans
• Immunocompromised Host
• Interleukin-4 (metabolism, pharmacology)
• Male
• Mice
• Mice, Nude
• Middle Aged
• Pancreatic Neoplasms (drug therapy, immunology, metabolism)
• Receptors, Interleukin-4 (biosynthesis, metabolism)
• Recombinant Fusion Proteins (metabolism, pharmacology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays