TAILIEUCHUNG - Báo cáo khoa học: A novel ErbB2 epitope targeted by human antitumor immunoagents

Two novel human antitumor immunoconjugates, engineered by fusion of a single-chain antibody fragment against human ErbB2 receptor, termed Erbicin, with either a human RNase or the Fc region of a human IgG1 , are selectively cytotoxic for ErbB2-positive cancer cellsin vitro andin vivo. | ijFEBS Journal A novel ErbB2 epitope targeted by human antitumor immunoagents Fulvia Troise1 2 Maria Monti3 2 Antonello Merlino4 5 Flora Cozzolino3 2 Carmine Fedele1 Irene Russo Krauss4 5 Filomena Sica4 5 Piero Pucci2 3 Giuseppe D Alessio1 and Claudia De Lorenzo1 2 1 Dipartimento di Biologia Strutturale e Funzionale Universita di Napoli Federico II Italy 2 CEINGE Biotecnologie avanzate Napoli Italy 3 Dipartimento di Chimica Organica e Biochimica Universita di Napoli Federico II Italy 4 Dipartimento di Chimica Universita di Napoli Federico II Italy 5 Istituto di Biostrutture e Bioimmagini CNR Naples Italy Keywords breast cancer cardiotoxicity ErbB2 Her2 Herceptin trastuzumab immunotherapy Correspondence C. De Lorenzo Dipartimento di Biologia Strutturale e Funzionale Universita di Napoli Federico II via Cinthia 80126 Napoli Italy Fax 39 081679159 Tel 39 081679158 E-mail cladelor@ These authors contributed equally to this work Received 13 December 2010 revised 24 January 2011 accepted 31 January 2011 doi Two novel human antitumor immunoconjugates engineered by fusion of a single-chain antibody fragment against human ErbB2 receptor termed Erbicin with either a human RNase or the Fc region of a human IgG1 are selectively cytotoxic for ErbB2-positive cancer cells in vitro and in vivo. These Erbicin-derived immunoagents EDIAs do not show the most negative properties of Herceptin the only humanized mAb against ErbB2 used in the therapy of breast carcinoma cardiotoxicity and the inability to act on resistant tumors. These differences are probably attributable to the different ErbB2 epitopes recognized by EDIAs and Herceptin respectively as we have previously reported that they induce different signaling mechanisms that control tumor and cardiac cell viability. Thus to accurately identify the novel epitope recognized by EDIAs three independent and complementary methodologies were used. They gave coherent results which are reported .

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