文章基本信息

标题：A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor
本地全文：下载
作者：Achim A. Jungbluth ; Elisabeth Stockert ; H. J. Su Huang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：2
页码：639-644
DOI：10.1073/pnas.232686499
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Epidermal growth factor receptor (EGFR) has attracted considerable attention as a target for cancer therapy. Wild-type (wt)EGFR is amplified/overexpressed in a number of tumor types, and several mutant forms of the coding gene have been found, with {Delta}EGFR, a deletion mutation lacking exons 2-7 of the external domain, being the most common and particularly associated with glioblastoma. We generated monoclonal antibodies (mAbs) against NR6{Delta}EGFR (mouse fibroblast line NR6 transfected with {Delta}EGFR). mAb 806 with selective reactivity for NR6{Delta}EGFR in mixed hemadsorption assays, fluorescence-activated cell sorting, Western blot, and immunohistochemistry was analyzed in detail and compared with mAbs 528 (anti-wtEGFR) and DH8.3 (anti-{Delta}EGFR). In xenograft tumors and molecularly pretyped glioblastomas, the reactivity pattern was as follows: 528 reactive with amplified and nonamplified wtEGFR; DH8.3 reactive with {Delta}EGFR; and 806 reactive with amplified/overexpressed wtEGFR (with or without {Delta}EGFR). In normal tissues, 528 but not DH8.3 or 806 was widely reactive with many organs, e.g., liver expressing high EGFR levels. In glioblastoma and non-CNS tumor panels, 806 was reactive with a high proportion of glioblastomas and a substantial number of epithelial cancers of lung and of head and neck. DH8.3 reactivity was restricted to {Delta}EGFR-positive glioblastoma. Thus, 806 represents a category of mAbs that recognizes tumors with EGFR amplification/overexpression but not normal tissues or tumors with normal EGFR levels. Our study also indicates that {Delta}EGFR is restricted to glioblastoma, in contrast to other reports that this mutation is found in tumors outside the brain.