Novel way to increase targeting specificity to a human glioblastoma‐associated receptor for interleukin 13
Novel way to increase targeting specificity to a human glioblastoma‐associated receptor for interleukin 13
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DOI：
10.1002/(sici)1097-0215(19980518)76:4
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发表时间：
1998-05
影响因子：
6.4
通讯作者：
W. Debinski;D. Gibo;R. Puri
中科院分区：
文献类型：
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作者：
W. Debinski;D. Gibo;R. Puri
人类脑癌(胶质瘤)过表达大量的白介素13受体(IL13)，使该受体成为抗胶质瘤治疗的一个有吸引力的靶点。我们最近提出，胶质瘤相关的IL13受体不同于一些造血细胞和体细胞上表达的受体。为了确定一个更具胶质瘤特异性的靶点，我们使用了相关细胞因子IL4的拮抗剂，它中和了IL13和IL4对正常细胞的生理影响。在这里，我们证明了IL4拮抗剂也抵消了针对IL13受体的细胞毒素对正常人类细胞的作用。重要的是，IL4拮抗剂根本不能抑制基于IL13的细胞毒素对胶质瘤细胞的作用。因此，在存在IL4拮抗剂的情况下，胶质瘤细胞上的IL13受体可以归类为肿瘤特异性受体。我们得出结论，IL13受体导向的细胞毒素可以被传递到胶质瘤细胞，而不会对正常细胞产生细胞毒性。内部J.癌症76：547-551,1998。
Human brain cancers (gliomas) overexpress large numbers of a receptor for interleukin 13 (IL13), making this receptor an attractive target for anti‐glioma therapies. We have recently proposed that the glioma‐associated IL13 receptor is different from the one expressed on some hemopoietic and somatic cells. In an attempt to identify an even more glioma‐specific target, we have used an antagonist of a related cytokine, IL4, which neutralizes the physiological effects of both IL13 and IL4 on normal cells. Here we demonstrate that the IL4 antagonist also counteracts the action of cytotoxins targeted to the IL13 receptor on normal human cells. Importantly, the IL4 antagonist does not inhibit IL13‐based cytotoxins on glioma cells at all. Thus, the IL13 receptor on glioma cells can be categorized as tumor‐specific in the presence of an IL4 antagonist. We conclude that IL13 receptor‐directed cytotoxins can be delivered to glioma cells without being cytotoxic to normal cells. Int. J. Cancer 76:547–551, 1998.© 1998 Wiley‐Liss, Inc.