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Article
November 1993

Transfer of Interleukin 2 Receptor Genes Into Squamous Cell Carcinoma: Modification of Tumor Cell Growth

Author Affiliations

From the Department of Pathology, University of Pittsburgh (Pa) School of Medicine, and Immunologic Monitoring and Diagnostic Laboratory, Pittsburgh Cancer Institute.

Arch Otolaryngol Head Neck Surg. 1993;119(11):1229-1235. doi:10.1001/archotol.1993.01880230075012
Abstract

Objective:  Human squamous cell carcinomas of the head and neck (SCCHN) have been shown to express interleukin 2 receptor (IL-2R), and binding of the ligand, IL-2, to the receptor results in tumor growth inhibition in vitro or in vivo in an SCCHN xenograft model in nude mice. To optimize growth inhibitory effects of IL-2, expression of the α or γ chains of IL-2R in SCCHN was experimentally modified by transfection of tumor cells with the respective IL-2R genes or the lacZ gene as control.

Design:  Using plasmid vectors containing the IL-2Rα chain gene under the control of a cytomegalovirus promoter or the IL-2Rγ chain gene under the control of a Rous sarcoma virus promoter, the IL-2R genes were transferred by lipofection into SCCHN cell lines. Stable transfectants were selected, cloned by limiting dilution, and clones were compared with the parental cell lines for their sensitivity to the growth-inhibitory effect of IL-2.

Results:  Transfer of the IL-2Rα chain gene into SCCHN cells resulted in significant upregulation of expression of the IL-2Rα chain on tumor cell surface but not in increased tumor growth inhibition by IL-2. In contrast, SCCHN IL-2Rγ transfectants, which expressed IL-2Rγ chain transcripts as confirmed in RNase protection assays, were significantly inhibited in growth and were sensitive to lower concentrations of IL-2 than the parental cell lines.

Conclusions:  Genetic modification of IL-2R expression on IL-2R—positive tumor cells in culture significantly alters their proliferative response to IL-2. These observations open a way for developing new strategies for therapy of SCCHN based on direct interactions of IL-2 with its receptor on tumor cells.(Arch Otolaryngol Head Neck Surg. 1993;119:1229-1235)

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