Effect of the anti-receptor ligand-blocking 225 monoclonal antibody on EGF receptor endocytosis and sorting

2006 ◽  
Vol 312 (15) ◽  
pp. 2778-2790 ◽  
Author(s):  
Maria L. Jaramillo ◽  
Zully Leon ◽  
Suzanne Grothe ◽  
Beatrice Paul-Roc ◽  
Abedelnasser Abulrob ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Egf Receptor ◽  
Receptor Ligand ◽  
Receptor Endocytosis

Abstract 4595: Development and validation of a novel EGF receptor-neutralizing monoclonal antibody

2016 ◽  
Author(s):  
Krystyna Zuberek Hincman ◽  
Christopher A. Manning ◽  
Michael R. Nelson ◽  
Michael Lewis ◽  
Roy Scialdone ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Egf Receptor ◽  
Neutralizing Monoclonal Antibody ◽  
Development And Validation

Characterization of monoclonal antibody CIBCNSH3 generated to the human EGF receptor

1999 ◽  
Vol 9 (3) ◽  
pp. 149-154
Author(s):  
Myleru Udayachander ◽  
Ananthanarayanan Meenakshi ◽  
Nallathambi Sivakumar ◽  
R. Ramesh Kumar ◽  
S.G. Vijay Shankar ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Egf Receptor

scholarly journals Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2385-2392 ◽  
Author(s):  
TM Walz ◽  
C Malm ◽  
BK Nishikawa ◽  
A Wasteson
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Transforming Growth Factor Alpha ◽  
Epidermal Growth ◽  
Factor Alpha

The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.

scholarly journals Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration

2015 ◽  
Vol 112 (43) ◽  
pp. 13225-13230 ◽  
Author(s):  
Sangwon Lee ◽  
Etienne B. Greenlee ◽  
Joseph R. Amick ◽  
Gwenda F. Ligon ◽  
Jay S. Lillquist ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tyrosine Kinases ◽  
Egf Receptor ◽  
Human Cancer ◽  
Extracellular Domain ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Fab Fragment ◽  
Allosteric Mechanism ◽  
Egfr Family

ErbB3 (HER3) is a member of the EGF receptor (EGFR) family of receptor tyrosine kinases, which, unlike the other three family members, contains a pseudo kinase in place of a tyrosine kinase domain. In cancer, ErbB3 activation is driven by a ligand-dependent mechanism through the formation of heterodimers with EGFR, ErbB2, or ErbB4 or via a ligand-independent process through heterodimerization with ErbB2 overexpressed in breast tumors or other cancers. Here we describe the crystal structure of the Fab fragment of an antagonistic monoclonal antibody KTN3379, currently in clinical development in human cancer patients, in complex with the ErbB3 extracellular domain. The structure reveals a unique allosteric mechanism for inhibition of ligand-dependent or ligand-independent ErbB3-driven cancers by binding to an epitope that locks ErbB3 in an inactive conformation. Given the similarities in the mechanism of ErbB receptor family activation, these findings could facilitate structure-based design of antibodies that inhibit EGFR and ErbB4 by an allosteric mechanism.

scholarly journals Influence of immunoglobulin isotype on therapeutic antibody function

Blood ◽  
2016 ◽  
Vol 127 (9) ◽  
pp. 1097-1101 ◽  
Author(s):  
Stephen A. Beers ◽  
Martin J. Glennie ◽  
Ann L. White
Keyword(s):  
Monoclonal Antibody ◽  
Cancer Treatment ◽  
Tumor Targeting ◽  
Therapeutic Antibody ◽  
Therapeutic Success ◽  
Receptor Ligand ◽  
Improve Outcome ◽  
Immunoglobulin Isotype ◽  
Antibody Function

Abstract Monoclonal antibody (mAb) therapeutics are revolutionizing cancer treatment; however, not all tumors respond, and agent optimization is essential to improve outcome. It has become clear over recent years that isotype choice is vital to therapeutic success with agents that work through different mechanisms, direct tumor targeting, agonistic receptor engagement, or receptor-ligand blockade, having contrasting requirements. Here we summarize how isotype dictates mAb activity and discuss ways in which this information can be used for the development of enhanced therapeutics.

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