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ISSN 0582-9879 Acta Biochim et Biophysica Sinica 2004, 36(6):437-442 CN 31-1300/Q

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Fusion Protein of Interleukin 4 and Diphtherial Toxin with High Cytotoxicity to Cancer Cells

Yu-Jian ZHANG, Xiao-Bo HU, Su-Xia LI1, Li-Ping TIAN, Sheng-Li YANG, and Yi GONG*

Research Center of Biotechnology, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200233, China;
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China

Abstract Receptor of human interleukin 4 (hIL4R) has been found to be present on many types of cancer, so it may be a good target for cancer therapy. Here, fusion toxin gene DT4H has been constructed by fusing DNA sequence encoding the first 389 amino acids of diphtherial toxin (DT), which can not bind its own receptor, to human interleukin 4 (hIL4) gene. In order to improve the affinity of fusion toxin for hIL4R, a circularly permuted form of hIL4 (cpIL4) was used. The fusion gene was expressed in Escherichia coli where the fusion toxin DT4H was highly expressed. Purified DT4H was very cytotoxic to cancer cell line U251 cells, and moderate cytotoxic to HepG2 and MCF-7 cells. SGC-7901 cells were insensitive to it. The cytotoxic action of DT4H was specific because it was blocked by excess hIL4. These results suggest that DT4H may be a useful agent in the treatment of certain malignancies.

Key words fusion toxin; diphtherial toxin; cancer therapy; interleukin 4; IL-4 receptor

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Received: February 9, 2004 Accepted: March 3, 2004

*Corresponding author: Tel, 86-21-54971069; Fax, 86-21-64700244; E-mail, [email protected]