Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes

被引：31

作者：

Cai, Z. ^{[1
]}

Zhang, G. ^{[1
]}

Zhou, Z. ^{[1
]}

Bembas, K. ^{[1
]}

Drebin, J. A. ^{[2
]}

Greene, M. I. ^{[1
]}

Zhang, H. ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Pathol Lab Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA

来源：

ONCOGENE | 2008年 / 27卷 / 27期

关键词：

her2; Pertuzumab; heterodimer; 4D5;

D O I：

10.1038/onc.2008.13

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

2C4 ( Pertuzumab, Omnitarg) is a monoclonal antibody targeting p185(her2/neu), which is overexpressed in 30% of invasive breast cancer. 2C4 is currently in phase II clinical trials for several types of cancers. This antibody has been reported to disrupt the association between p185(her2/neu) and ErbB3. In our studies of epidermal growth factor receptor ( EGFR)-p185(her2/neu) heterodimerization, we noted that 2C4 formed associations with the EGFR-p185(her2/neu) receptor complex. Our data argue against 2C4 as a universal heterodimerization blocker for p185(her2/neu), but indicate that cocktails of monoclonal antibodies binding distinct interaction surfaces of p185(her2/neu) will emerge as the most potent targeted therapy.

引用

页码：3870 / 3874

页数：5

共 30 条

[1] Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth [J].

Agus, DB ;

Akita, RW ;

Fox, WD ;

Lewis, GD ;

Higgins, B ;

Pisacane, PI ;

Lofgren, JA ;

Tindell, C ;

Evans, DP ;

Maiese, K ;

Scher, HI ;

Sliwkowski, MX .

CANCER CELL, 2002, 2 (02) :127-137

[2] Disabling receptor ensembles with rationally designed interface peptidomimetics [J].

Berezov, A ;

Chen, JQ ;

Liu, QD ;

Zhang, HT ;

Greene, MI ;

Murali, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (31) :28330-28339

[3] HUMANIZATION OF AN ANTI-P185HER2 ANTIBODY FOR HUMAN CANCER-THERAPY [J].

CARTER, P ;

PRESTA, L ;

GORMAN, CM ;

RIDGWAY, JBB ;

HENNER, D ;

WONG, WLT ;

ROWLAND, AM ;

KOTTS, C ;

CARVER, ME ;

SHEPARD, HM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4285-4289

[4] Structure of the extracellular region of HER3 reveals an interdomain tether [J].

Cho, HS ;

Leahy, DJ .

SCIENCE, 2002, 297 (5585) :1330-1333

[5] Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab [J].

Cho, HS ;

Mason, K ;

Ramyar, KX ;

Stanley, AM ;

Gabelli, SB ;

Denney, DW ;

Leahy, DJ .

NATURE, 2003, 421 (6924) :756-760

[6]

COHEN JA, 1989, ONCOGENE, V4, P81

[7] DOWN-MODULATION OF AN ONCOGENE PROTEIN PRODUCT AND REVERSION OF THE TRANSFORMED PHENOTYPE BY MONOCLONAL-ANTIBODIES [J].

DREBIN, JA ;

LINK, VC ;

STERN, DF ;

WEINBERG, RA ;

GREENE, MI .

CELL, 1985, 41 (03) :695-706

[8]

DREBIN JA, 1988, ONCOGENE, V2, P273

[9] MONOCLONAL-ANTIBODIES IDENTIFY A CELL-SURFACE ANTIGEN ASSOCIATED WITH AN ACTIVATED CELLULAR ONCOGENE [J].

DREBIN, JA ;

STERN, DF ;

LINK, VC ;

WEINBERG, RA ;

GREENE, MI .

NATURE, 1984, 312 (5994) :545-548

[10] EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization [J].

Ferguson, KM ;

Berger, MB ;

Mendrola, JM ;

Cho, HS ;

Leahy, DJ ;

Lemmon, MA .

MOLECULAR CELL, 2003, 11 (02) :507-517

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