PMID: 15383606Sep 24, 2004Paper

Dual mode of action of a human anti-epidermal growth factor receptor monoclonal antibody for cancer therapy

The Journal of Immunology : Official Journal of the American Association of Immunologists
Wim K BleekerPaul W H I Parren

Abstract

Epidermal growth factor receptor (EGF-R) overexpression is common in a large number of solid tumors and represents a negative prognostic indicator. Overexpression of EGF-R is strongly tumor associated, and this tyrosine kinase type receptor is considered an attractive target for Ab therapy. In this study, we describe the evaluation of mAb 2F8, a high avidity human mAb (IgG1kappa) directed against EGF-R, developed using human Ig transgenic mice. mAb 2F8 effectively blocked binding of EGF and TGF-alpha to the EGF-R. At saturating concentrations, 2F8 completely blocked EGF-R signaling and inhibited the in vitro proliferation of EGF-R-overexpressing A431 cells. At much lower concentrations, associated with low receptor occupancy, 2F8 induced efficient Ab-dependent cell-mediated cytotoxicity (ADCC) in vitro. In vivo studies showed potent antitumor effects in models with A431 tumor xenografts in athymic mice. Ex vivo analysis of the EGF-R status in tumor xenografts in 2F8-treated mice revealed that there are two therapeutic mechanisms. First, blocking of EGF-R signaling, which is most effective at complete receptor saturation and therefore requires a relatively high Ab dose. Second, at very low 2F8 receptor occupancy, we observed pot...Continue Reading

References

Jan 1, 1988·Annual Review of Immunology·J C UnkelessV H Freedman
Oct 1, 1988·European Journal of Immunology·C I BindonH Waldmann
Jun 27, 1985·The New England Journal of Medicine·T MeekerR Levy
Mar 4, 1982·The New England Journal of Medicine·R A MillerR Levy
Jul 1, 1995·Critical Reviews in Oncology/hematology·D S SalomonN Normanno
Oct 1, 1994·Pharmacology & Therapeutics·J Baselga, J Mendelsohn
Aug 18, 1993·Journal of the National Cancer Institute·J BaselgaJ Mendelsohn
Jul 31, 1998·Immunogenetics·W van der Pol, J G van de Winkel
Oct 6, 1999·Current Opinion in Immunology·M S CraggM J Glennie
Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Mar 20, 2001·Critical Reviews in Oncology/hematology·X D YangC G Davis
Jun 28, 2001·Oncogene·J Mendelsohn, J Baselga
Jul 27, 2001·Current Opinion in Chemical Biology·M A van Dijk, J G van de Winkel
Sep 22, 2001·Biomolecular Engineering·A A KorttP J Hudson
Mar 22, 2003·Experimental Cell Research·H Steven Wiley
Mar 22, 2003·Experimental Cell Research·Carlos L Arteaga
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eirikur SaelandJan G J Van De Winkel
Jun 24, 2003·Drug Discovery Today·Martin J Glennie, Jan G J van de Winkel

❮ Previous
Next ❯

Citations

Nov 23, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Francisco RobertMichael Needle
Jun 2, 2006·Cancer Immunology, Immunotherapy : CII·Rob C RooversPaul M P van Bergen en Henegouwen
Mar 30, 2007·Nature Clinical Practice. Oncology·Alejandro D Ricart, Anthony W Tolcher
Sep 18, 2007·Science·Marijn van der Neut KolfschotenPaul W H I Parren
Feb 13, 2008·European Journal of Nuclear Medicine and Molecular Imaging·M Jules Mattes, David M Goldenberg
Apr 20, 2010·Head & Neck Oncology·Martin GoernerHolger Sudhoff
Nov 26, 2010·The Mount Sinai Journal of Medicine, New York·Stacey J Baker, E Premkumar Reddy
Mar 6, 2012·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Mette K NedergaardHans S Poulsen
Jun 9, 2015·Cytometry. Part B, Clinical Cytometry·Meina LiangLorin K Roskos
Jun 14, 2006·Critical Reviews in Clinical Laboratory Sciences·Finn Edler von Eyben
Nov 23, 2006·Assay and Drug Development Technologies·Joakim Glamann, Anker Jon Hansen
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthias PeippThomas Valerius
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tanja Schneider-MerckMichael Dechant
Dec 22, 2009·Future Oncology·Maija Hollmén, Klaus Elenius
Aug 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aran F LabrijnPaul W H I Parren
Jun 2, 2017·International Journal of Cancer. Journal International Du Cancer·Satoshi OkazakiHeinz-Josef Lenz
Aug 15, 2008·Biotechnology Journal·Sigrid R RuulsPaul W H I Parren
Apr 22, 2009·Expert Opinion on Biological Therapy·Fernando RiveraCarlos López
Sep 10, 2005·Nature Biotechnology·Nils Lonberg
Feb 17, 2009·Current Oncology Reports·Steve C LeeRobert L Ferris
Dec 29, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michel de WeersPaul W H I Parren
Jun 26, 2009·Journal of Pharmacokinetics and Pharmacodynamics·Ben-Fillippo KrippendorffWilhelm Huisinga
Jan 12, 2011·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A B BohnM E Hokland
Sep 8, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marije B OverdijkPaul W H I Parren
Mar 9, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Ben-Fillippo KrippendorffWilhelm Huisinga
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Aran F LabrijnPaul W H I Parren
Jul 19, 2016·Expert Review of Proteomics·Rebecca Christine Feiner, Kristian Mark Müller
May 5, 2016·Expert Opinion on Investigational Drugs·Hasain Iqbal, Quintin Pan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex, associated with a generally dismal prognosis owing to its aggressive behavior. Here are the latest discoveries pertaining to this disease.

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.