Interleukin 4 receptor-directed cytotoxin therapy for human head and neck squamous cell carcinoma in animal models

Scott E. Strome, Koji Kawakami, Danielle Alejandro, Stephen Voss, Jan L. Kasperbauer, Diva Salomao, Lieping Chen, Richard A. Maki, Raj K. Puri

Research output: Contribution to journalArticle

Abstract

Receptors for interleukin 4 (IL-4R) are overexpressed on the surface of various human solid tumors including renal cell carcinoma, glioblastoma, Kaposi's sarcoma, and head and neck squamous cell carcinoma (SCCHN). On the basis of this preferential receptor overexpression, a novel IL-4R-targeted cytotoxin, IL-4 (38-37)-PE38KDEL, was developed in which circularly permuted IL-4 [IL-4 (38-37)] was fused to mutated form of Pseudomonas exotoxin (PE38KDEL). Despite the recognized expression of the IL-4R on SSCHN, the utility of a receptor-specific fusion protein for the treatment of this disease remains unknown. The purpose of this study was to establish the utility of IL-4 (38-37)-PE38KDEL for the treatment of established SSCHN in animal models of human disease. Expression of IL-4R in SCCHN was confirmed by immunohistochemistry with eight of eight tissue sections expressing IL-4R. Protein synthesis inhibition assays demonstrated growth inhibition of two cell lines in IL-4 (38-37)-PE38KDEL in a dose-dependent fashion. In two SCCHN s.c. xenografted nude mouse models, i.p. and intratumoral injection of IL-4 (38-37)-PE38KDEL mediated tumor regression with no visual toxicity observed in any of the animals. Subcultured tumor cells after intratumoral treatment with IL-4 toxin did not develop resistance to the drug. These data demonstrate that IL-4 (38-37)-PE38KDEL is effective in mediating significant antitumor effects in SCCHN and may represent an attractive therapeutic option for patients with advanced cancers of the upper aerodigestive tract.

Original languageEnglish (US)
Pages (from-to)281-286
Number of pages6
JournalClinical Cancer Research
Volume8
Issue number1
Publication statusPublished - 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Strome, S. E., Kawakami, K., Alejandro, D., Voss, S., Kasperbauer, J. L., Salomao, D., ... Puri, R. K. (2002). Interleukin 4 receptor-directed cytotoxin therapy for human head and neck squamous cell carcinoma in animal models. Clinical Cancer Research, 8(1), 281-286.