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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2009, Vol. 29 Issue (04): 98-103    
综述     
IL-13Rα2介导的毒素融合蛋白在肿瘤治疗中的应用
杜娟,胡红刚,侯玲玲
 北京交通大学理学院生物科学与技术研究所
Application of IL-13Rα2-directed Toxin Fusion Protein in Tumor Therapy
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摘要： 近年来IL-13受体IL-13Rα2的研究已经成为一个新兴热点，IL-13Rα2在许多肿瘤细胞细胞表面存在特异性高表达，而在正常组织中不表达或表达量很低，通过IL-13Rα2介导的毒素融合蛋白靶向治疗肿瘤也已成为肿瘤诊断和免疫治疗研究中的重要方面。随着对IL-13Rα-结构和功能及其与肿瘤关系研究的不断深入，将为肿瘤的靶向治疗提供新的思路，为肿瘤的临床治疗提供新的理论依据。对IL-13Rα2在不同肿瘤中的表达及IL-13和不同毒素融合得到的毒素融合蛋白在细胞和动物体内等不同水平上对肿瘤治疗的作用做出了相应概括，并对通过IL-13Rα2介导的毒素融合蛋白治疗肿瘤机理的研究以及融合蛋白方法改进及其它相关治疗方法等方面作出综述。
关键词： 癌症;IL-13Rα2;肿瘤靶向治疗    
Abstract: The research of interleukin13 receptor α2 (IL-13Rα2) chain is a rising pop these years. Previous studies have shown that many human tumors overexpress IL-13Rα2 chain, while normal cells do not express this receptor or express very low level. This difference of express level is significant to diagnose and cure tumors by the IL-13Rα2-directed toxin fusion protein. During the past decade, the structure and the function of IL-13Rα2 together with the relationship between this receptor and tumors has been further developed. Therefore new therapies and theories can be proposed as the clinical tumor treatments. In this case,the expression in various tumor cell lines was not only focused on but also on the IL-13 and toxin fusion protein killing effect in both the cell level and the in vivo level. Besides,an overview of the mechanism in the treatment of IL-13Rα2-directed toxin fusion protein together with the improved methods for fusion protein purification and other relative tumor therapy was given. In conclusion,the current status and progress of IL-13Rα2 as well as IL-13Rα2-directed toxin fusion protein in tumor therapy were represented.
Key words: Carcinoma;IL-13Rα2;Tumor therapy;Progress
收稿日期: 2008-09-05 出版日期: 2009-04-27
ZTFLH:  Q279  
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通讯作者: 侯玲玲   
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杜娟 胡红刚 侯玲玲

引用本文:

杜娟,胡红刚,侯玲玲. IL-13Rα2介导的毒素融合蛋白在肿瘤治疗中的应用[J]. 中国生物工程杂志, 2009, 29(04): 98-103.

DU Juan- Hu-Gong-Gang- Hou-Ling-Ling. Application of IL-13Rα2-directed Toxin Fusion Protein in Tumor Therapy. China Biotechnology, 2009, 29(04): 98-103.

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https://manu60.magtech.com.cn/biotech/CN/    或    https://manu60.magtech.com.cn/biotech/CN/Y2009/V29/I04/98

［1］ Lebman D A, Coffman R L. Interleukine-4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures. J Exp Med, 1988, 168(3): 853~862 ［2］ Ihle J N, Witthuhn B A, Quelle F W, et al. Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol, 1995, 13(1): 369~398 ［3］ Rahaman S O, Sharma P, Harbor P C, et al. IL-13Rα2, a decoy receptor for IL-13 acts as an inhibitor or IL-4-dependent signal transduction in glioblastoma cells. Cancer Research, 2002, 62(4): 1103~1109 ［4］ Nelms K, Keegan A D, Zamorano J, et al. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol, 1999, 17(1): 701~738 ［5］ Joshi B H, Plautz G E,Puri R K. Interleukin-13 receptor α chain: A novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Research, 2000, 60(5): 1168~1172 ［6］ Kawakami M, Kawakami K, Kasperbauer J L, et al. Interleukin-13 receptor α2 chain in human head and neck cancer serves as a unique diagnostic marker. Clin Cancer Research, 2003, 9(17): 6381~6388 ［7］ Kawakami M, Kawakami K, Takahashi S, et al. Analysis of interleukin13 receptor α2 expression in human pediatric brain tumors. Cancer, 2004, 101(5): 1036-1042 ［8］ Kioi M, Kawakami M, Shimamura T, et al. Interleukin13 receptor α2 china a potential biomarker and molecular target for ovarian cancer therapy. Cancer, 2006, 107(6): 1407~1418 ［9］ Obiri N I, Debinski W, Leonard W J, et al. Receptor for interleukin 13. Interaction with interleukin 4 by a mechanism that does not involve the common gamma chain shared by receptors for interleukins 2, 4, 7, 9, and 15. J Biol Chem, 1995, 270(15): 8797~8804 ［10］ Debinski W, Obiri N I, Powers S K, et al. A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J Biol Chem, 1995, 270(28): 16775~16780 ［11］ Obiri N I, Leland P, Murata T. The IL-13 receptor structure differs on various cell types and may share more than one component with IL-4 receptor. J Immunol, 1997, 158(2): 756~764 ［12］ Husain S R, Puri R K. Interleukin13 fusion cytotoxin as a potent targeted agent for AIDSKaposi’s sarcoma xenograft. Blood, 2000, 95(11): 3506~3513 ［13］ Maini A, Hillman G, Haas G P, et al. Interleukin13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL13 and a mutated form of Pseudomonas exotoxin. J Urol, 1997, 158(3 Pt 1): 948~953 ［14］ Kornmann M, Kleeff J, Debinski W, et al. Pancreatic cancer cells express interleukin13 and 4 receptors, and their growth is inhibited by Pseudomonas exotoxin coupled to interleukin13 and 4. Anticancer Res, 1999, 19(1A): 125~131 ［15］ Debinski W, Obiri N I, Powers S K, et al. Human glioma cells overexpress receptors for interleukin 13 and are Extremely sensitive to a novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin. Clin Cancer Research, 1995, 1(11): 1253~1258 ［16］ Husain S R, Obiri N I, Gill P, et al. Receptor for interleukin 13 on AIDSassociated Kaposi’s sarcoma cells serves as a new target for a potent Pseudomonas exotoxinbased chimeric toxin protein. Clin Cancer Research, 1997, 3(2): 151~156 ［17］ Puri R K, Leland P, Obiri N I, et al. Targeting of interleukin13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin13 and a truncated form of Pseudomonas exotoxin A (PE38QQR). Blood, 1996, 87(10): 43334339 ［18］ Husain S R, Joshi B H, Puri R K. Interleukin13 receptor as a unique target for antiglioblastoma therapy. Int J Cancer, 2001, 92(2): 168~175 ［19］ Debinski W, Gibo D M, Obiri N I，et al. Novel antibrain tumor cytotoxins specific for cancer cells. Nat Biotechnol, 1998, 16(5): 449~453 ［20］ Debinski W, Gibo D M, Puri R K. Novel way to increase targeting specificity to a human glioblastomaassociated receptor for interleukin 13. Int J Cancer, 1998, 76(4): 547~551 ［21］ Li C, Hall W A, Jin N, et al. Targeting glioblastoma multiforme with an IL13/diphtheria toxin fusion protein in vitro and in vivo in nude mice. Protein Engineering, 2002, 15(5): 419~427 ［22］ Mintz A, Gibo D M, SlagleWebb B, et al. IL13Rα2 is a Gliomarestricted receptor for interleukin13. Neoplasia, 2002, 4(5): 388~399 ［23］ Kawakami K, Kawakami M, Sony P J, et al. In vivo overexpression of IL13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J Exp Med, 2001, 194(12): 1743~1754 ［24］ Kawakami K, Kioi M, Liu Q, et al. Evidence that IL13Rα2 chain in human glioma cells is responsible for the antitumor activity mediated by receptordirected cytotoxin therapy. J Immunother, 2005, 28(3): 193~202 ［25］ LeMaistre C F, Saleh M N, Kuzel T M, et al. Phase Ⅰ trial of ligand fusionprotein (DAB389IL2) in lymphomas expressing the receptor for interleukin2. Blood, 1998, 91(2): 399~405 ［26］ Kawakami K, Kawakami M,Puri R K.Specifically targeted killing of interleukin13(IL13) receptorexpressing breast cancer by IL13 fusion cytotoxin in animal model of human disease. Molecular Cancer Therapeutics, 2004, 3(2): 137~147 ［27］ Weingart J, Strauss L C, Grossman S A, et al. Phase Ⅰ/Ⅱ study: intratumoral infusion of IL13PE38QQR cytotoxin for recurrent supratentorial malignant glioma. NeuroOncology, 2002, 4: 379 ［28］ Wu Ah,Low W C. Molecular cloning of the rat IL13 alpha 2 receptor cDNA and its expression in rat tissues. Journal of NeuroOncology, 2002, 59(2): 99~105 ［29］ Mintz A, Gibo D M, Madhankumar A B, et al. Molecular targeting with recombinant cytotoxins of interleukin13 receptor α2expressing glioma. Journal of NeuroOncology, 2003, 64(1): 117~123 ［30］ Joshi B H, Puri R K. Optimization of expression and purification of two biologically active chimeric fusion proteins that consist of human interleukin13 and Pseudomonas exotoxin in Escherichia coli. Protein Expression and Purification, 2005, 39(2): 189~198 ［31］ Zhou G, Roizman B. Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL13 {alpha} 2 receptor. PNAS, 2006, 103(14): 5508~5513 ［32］ Murata T, Obiri N I, Debinski W, et al. Structure of IL13 receptor: analysis of subunit composition in cancer and immune cells. Biochem Biophy Res Commun, 1997, 238(1): 90~94 ［33］ Oshima Y, Puri R K. Suppression of an IL13 autocrine growth loop in a human Hodgkin/ReedSternberg tumor cell line by a novel IL13 antagonist. Cell Immunology, 2001, 211(1): 37~42 ［34］ Oshima Y, Puri R K. Characterization of a powerful high affinity antagonist that inhibits biological activities of human interleukin13. J Biol Chem, 2001, 276(18): 15185~15191 ［35］ Honjo Y, Bian Y, Kawakami K, et al. TGFbeta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma. Cell Cycle, 2007, 6(11): 1360~1366 ［36］ Kawakami M, Kawakami K,Puri R K.Tumor regression mechanisms by IL13 receptortargeted cancer therapy involve apoptotic pathways. Int J Cancer, 2003, 103(1): 45~52 ［37］ Han J, Yang L, Puri R K. Analysis of target genes induced by IL13 cytotoxin in human glioblastoma cells. Journal of NeuroOncology, 2005, 72(1): 35~46 ［38］ Kioi M, Seetharam S, Puri R K. Nlinked glycosylation of IL13Rα2 is essential for optimal IL13 inhibitory activity. Faseb J, 2006, 20(13): 2378~2380
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