Skip Navigation



Carcinogenesis Advance Access published online on June 1, 2005
Carcinogenesis, doi:10.1093/carcin/bgi146
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/11/1890    most recent
bgi146v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by De Lorenzo, C.
Right arrow Articles by D'Alessio, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by De Lorenzo, C.
Right arrow Articles by D'Alessio, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received March 2, 2005
Revised April 26, 2005
Accepted May 29, 2005

CANCER BIOLOGY

Biological properties of a human compact anti-ErbB2 antibody

Claudia De Lorenzo 1, Rosanna Cozzolino 1, Andrea Carpentieri 2, Piero Pucci 2, Paolo Laccetti 1, and Giuseppe D'Alessio 1*

1 Department of Structural and Functional Biology, University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy
2 Department of Organic Chemistry and Biochemistry, University of Naples "Federico II", Via Cinthia, 80126 Naples, Italy

* To whom correspondence should be addressed.
Giuseppe D'Alessio, E-mail: dalessio{at}unina.it


  Abstract

ErbB2 is a prognostic factor and target of therapy for many carcinomas. In contrast with the other ErbB receptors, ErbB2 lacks a soluble direct ligand, but it is the preferred co-receptor for the ErbB family members, forming heterodimers with more potent and prolonged signalling activity than that of homodimers. We recently produced a new anti-ErbB2 antibody, Erb-hcAb, by fusion of Erbicin, a human, anti-ErbB2 scFv, selectively cytotoxic to ErbB2-positive cells, and a human Fc domain. This fully human antitumour antibody represents a compact version of an IgG1, with the cytotoxicity of the scFv moiety on target cells, combined with the ability of the Fc moiety to induce both antibody- and complement-dependent cytotoxicity.

Here we describe the main properties of Erb-hcAb, using as a reference Herceptin, an anti-ErbB2 humanized monoclonal currently employed in clinical immunotherapy. We found that both bivalent Erb-hcAb and Herceptin increase receptor phosphorylation and downregulation, whereas monovalent Erbicin does not. These results correlate with the finding that Erb-hcAb is capable of inducing apoptosis and inhibiting cell cycle progression in ErbB2-positive cells. Its powerful in vitro antitumour action matched that observed in vivo in experiments with human ErbB2-positive tumour xenografts established in athymic mice. Finally, Erb-hcAb displays a glycosylation profile virtually superimposable to that of a human IgG. These findings suggest that Erb-hcAb is a very promising new agent for the immunotherapy of carcinomas that overexpress the ErbB2 receptor.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
G. Riccio, G. Esposito, E. Leoncini, R. Contu, G. Condorelli, M. Chiariello, P. Laccetti, S. Hrelia, G. D'Alessio, and C. De Lorenzo
Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents
FASEB J, September 1, 2009; 23(9): 3171 - 3178.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Kubetzko, E. Balic, R. Waibel, U. Zangemeister-Wittke, and A. Pluckthun
PEGylation and Multimerization of the Anti-p185HER-2 Single Chain Fv Fragment 4D5: EFFECTS ON TUMOR TARGETING
J. Biol. Chem., November 17, 2006; 281(46): 35186 - 35201.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.