Journal Article

Biological properties of a human compact anti-ErbB2 antibody

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

in Carcinogenesis

Volume 26, issue 11, pages 1890-1895
Published in print November 2005 | ISSN: 0143-3334
Published online June 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi146
Biological properties of a human compact anti-ErbB2 antibody

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  • Clinical Cytogenetics and Molecular Genetics

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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.

Keywords: ADCC, antibody-dependent cellular cytotoxicity; CDC, complement-dependent cytotoxicity; Erb-hcAb, Erbicin-derived human, compact antibody; FACS, fluorescence-activated cell sorting; FITC, fluorescein-isothiocyanate; HRP, horseradish peroxidase; mAb, monoclonal antibody; MALDI, matrix-assisted laser desorption ionization; PBS, phosphate-buffered saline; PNGase F, peptide N-glycosidase F; PSD, post source decay; scFv, single chain variable fragment

Journal Article.  4575 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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