Targeting interleukin-4 receptors for effective pancreatic cancer therapy.
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.
Kawakami
Koji
K
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Kawakami
Mariko
M
Husain
Syed R
SR
Puri
Raj K
RK
D000328:Adult; D000368:Aged; D000818:Animals; D005098:Exotoxins / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D005098:Exotoxins; C059989:IL-4-PE40 protein, recombinant; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4