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Carcinogenesis Advance Access originally published online on June 1, 2005
Carcinogenesis 2005 26(11):1890-1895; doi:10.1093/carcin/bgi146
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Carcinogenesis vol.26 no.11 © Oxford University Press 2005; all rights reserved.

Biological properties of a human compact anti-ErbB2 antibody

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

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

* To whom correspondence should be addressed. Tel: +39 081 2534731; Fax: +39 081 5521217; Email: dalessio{at}unina.it

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.


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