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- Title
Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor a2 chain in vivo.
- Authors
Kawakami, K; Kawakami, M; Husain, S R; Puri, R K
- Abstract
Interleukin-13 receptor (IL-13R) α2 chain plays a key role in ligand binding and internalization. We have recently demonstrated that this cytokine receptor chain has unique characteristics in tumor biology: it inhibits tumorigenicity of breast and pancreatic cancer in animal models. In this study, we have exploited IL-13Rα2 chain and established a novel approach for pancreatic cancer therapy. For this, a plasmid encoding the IL-13Rα2 chain gene was mixed with liposomes and injected into subcutaneously or orthotopically xeno-grafted human pancreatic tumors in immunodeficient mice, followed by systemic or local therapy by a recombinant IL-13 cytotoxin. Only tumors forced to express IL-13Rα2 chain acquired extreme susceptibility to the antitumor effect of IL-13 cytotoxin. There was a dominant infiltration of cells including macrophages and natural killer cells in the regressing tumors. Since macrophages were found to produce nitric oxide, IL-13Rα2-targeted cancer therapy involved not only a direct tumor cell killing by IL-13 cytotoxin but also activation of innate immune response at the tumor site. Therefore, this approach may be a new powerful tool for pancreatic cancer or other localized cancer therapy.
- Subjects
INTERLEUKINS; CYTOKINES; CANCER treatment; MACROPHAGES; IMMUNE response
- Publication
Gene Therapy, 2003, Vol 10, Issue 13, p1116
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301956