HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Robert B. Cameron David M. Jablons Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Beseth, B. D. Articles by Puri, R. K. Search for Related Content PubMed PubMed Citation Articles by Beseth, B. D. Articles by Puri, R. K. Related Collections Pleura

Ann Thorac Surg 2004;78:436-443
© 2004 The Society of Thoracic Surgeons

---

Original article: general thoracic

Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts

^a Section of General Thoracic Surgery, University of California, Los Angeles, California, USA
^b Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapy, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Bethesda, Maryland, USA
^c Division of Biostatistics, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
^d Laboratory of Molecular Biology, National Cancer Institutes, National Institutes of Health, Bethesda, Maryland, USA
^e Neurocrine Biosciences, San Diego, California, USA

Accepted for publication June 3, 2003.

^* Address reprint requests to Dr Cameron, Thoracic Surgery, Department of Surgery, UCLA School of Medicine, 10833 Le Conte Ave, Room 62-215 CHS, PO Box 951741, Los Angeles, CA 90095-1741, USA
e-mail: rcameron{at}mednet.ucla.edu

Presented at the Thirty-ninth Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2003.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an uncommon but highly fatal neoplasm for which only limited treatment is available.

METHODS: Immunohistochemical analysis was used to determine the expression of interleukin-4 receptors (IL-4R) on mesothelioma cell lines and resected mesothelioma tumors. Radioreceptor binding assays were used to show that these IL-4R were high-affinity receptors. Previously, we had shown that a chimeric protein composed of a circularly permuted IL-4 molecule fused to a truncated form of Pseudomonas exotoxin A, IL-4(38–37)-PE38KDEL, could be used to kill IL-4R–bearing tumor cells in vitro. The toxicity of this molecule to mesothelioma cell lines was tested using a protein synthesis inhibition assay. A human mesothelioma xenograft model was then developed to assess the efficacy of this molecule in vivo.

RESULTS: All MPM cell lines tested were found to express high-affinity cell-surface IL-4R. Immunohistochemical analysis of resected mesothelioma tumor specimens from 13 patients revealed that all tumors expressed moderate-to-high levels of IL-4R. Coculture of malignant mesothelioma cell lines with IL-4(38–37)-PE38KDEL resulted in a dose-dependent inhibition of tumor cell protein synthesis through an interaction with cell-surface IL-4R. In a nude mouse xenograft model of human MPM, intratumoral administration of IL-4(38–37)-PE38KDEL mediated a dose-dependent decrease in tumor volume and a dose-dependent increase in survival.

CONCLUSIONS: The chimeric protein, IL-4(38–37)-PE38KDEL, has potent antitumor effects against MPM both in vitro and in vivo.