SPECIFIC TARGETING OF A MUTANT, ACTIVATED EGF RECEPTOR FOUND IN GLIOBLASTOMA USING A MONOCLONAL-ANTIBODY
SPECIFIC TARGETING OF A MUTANT, ACTIVATED EGF RECEPTOR FOUND IN GLIOBLASTOMA USING A MONOCLONAL-ANTIBODY
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DOI：
10.1002/ijc.2910630414
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发表时间：
1995-11-15
影响因子：
6.4
通讯作者：
GULLICK, WJ
中科院分区：
文献类型：
--
作者：
HILLS, D;ROWLINSONBUSZA, G;GULLICK, WJ
截短的表皮生长因子受体（EGFR）是由EGFR基因重排和扩增后表达的，在胶质瘤中出现的频率很高。在这项工作中，我们表明，当这种受体在NIH 3 T3成纤维细胞中表达时，它被部分激活，并赋予该细胞系在体内的致瘤性，但在体外锚定非依赖性生长试验中没有生长优势。由于突变发生在受体的细胞外结构域，因此可以认为它代表了神经胶质瘤特异性肿瘤标志物。在这里，我们证明了2个单克隆抗体，DHI.I和DH8.3，提出了一个合成肽跨越独特的交界序列，可以识别的突变受体，但不是在变性和天然状态下的正常受体。此外，放射性标记的抗体DH8.3成功靶向裸鼠中表达该抗原的肿瘤。(C)1995 Wiley-Liss，Inc.
A truncated epidermal growth factor receptor (EGFR) expressed from a rearranged and amplified EGFR gene is present at high frequency in gliomas. In this work we show that when this receptor is expressed in NIH3T3 fibroblasts it is partially activated and confers tumorigenicity to this cell line in vivo but no growth advantage in in vitro anchorage-independent growth assays. Because the mutation occurs in the extracellular domain of the receptor, it can be considered to represent a glioma-specific tumour marker. Here we demonstrate that 2 monoclonal antibodies, DHI.I and DH8.3, raised to a synthetic peptide spanning the unique junctional sequence, can recognise the mutant receptor but not the normal receptor in both denatured and native states. Furthermore, radiolabelled antibody DH8.3 successfully targets tumours expressing this antigen in nude mice. (C) 1995 Wiley-Liss, Inc.