A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor

Jungbluth, Achim A. and Stockert, Elisabeth and Huang, H.J. Su and Collins, Vincent P. and Coplan, Keren and Iversen, Kirstin and Kolb, Denise and Johns, Terrance J. and Scott, Andrew M. and Gullick, William J. and Ritter, Gerd and Cohen, Leonard and Scanlan, Matthew J. and Cavenee, Webster K. and Old, Lloyd J. (2003) A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor. Proceedings of the National Academy of Sciences USA, 100 (2). pp. 639-644. ISSN 0027-8424. (doi:https://doi.org/10.1073/pnas.232686499) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

Abstract

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 DeltaEGFR, 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(DeltaEGFR) (mouse fibroblast line NR6 transfected with DeltaEGFR). mAb 806 with selective reactivity for NR6(DeltaEGFR) 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-DeltaEGFR). In xenograft tumors and molecularly pretyped glioblastomas, the reactivity pattern was as follows: 528 reactive with amplified and nonamplified wtEGFR; DH8.3 reactive with DeltaEGFR; and 806 reactive with amplified/overexpressed wtEGFR (with or without DeltaEGFR). 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 DeltaEGFR-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 DeltaEGFR is restricted to glioblastoma, in contrast to other reports that this mutation is found in tumors outside the brain.

Item Type:	Article
Uncontrolled keywords:	Animals Antibodies, Monoclonal/*therapeutic use Glioblastoma/chemistry/therapy Humans Mice Mice, Inbred BALB C Neoplasm Transplantation Neoplasms/chemistry/*therapy Receptor, Epidermal Growth Factor/analysis/*genetics/*immunology Transplantation, Heterologous Tumor Cells, Cultured
Subjects:	Q Science R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculties > Sciences > School of Biosciences > Biomedical Research Group
Depositing User:	Bill Gullick
Date Deposited:	03 Sep 2008 23:44 UTC
Last Modified:	07 Aug 2018 08:51 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/3982 (The current URI for this page, for reference purposes)