A novel ErbB2 epitope targeted by human antitumor immunoagents(403 views) Troise F, Monti M, Merlino A, Cozzolino F, Fedele C, Russo Krauss I, Sica F, Pucci P, D'Alessio G, De Lorenzo C
Keywords: Breast Cancer, Cardiotoxicity, Erbb2 Her2, Herceptin Trastuzumab, Immunotherapy, Antineoplastic Agent, Epidermal Growth Factor Receptor 2, Epidermal Growth Factor Receptor 2 Human Compact Antibody, Epitope, Erbicin, Erbicin Ribonuclease Fusion Protein, Pertuzumab, Unclassified Drug, Amino Acid Sequence, Article, Binding Assay, Controlled Study, Drug Receptor Binding, Drug Screening, Enzyme Linked Immunosorbent Assay, Epitope Mapping, Extracellular Space, Mass Spectrometry, Molecular Docking, Priority Journal, Protein Degradation, Animals, Antibodies, Monoclonal, Breast Neoplasms, Computer Simulation, Female, Immunoconjugates, Models, Molecular Sequence Data, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins, Tumor Cells, Cultured, Immunology, Therapeutic Use, Humanized, Chemistry Immunology Therapeutic Use, Drug Therapy, Erbb-2 Immunology,
Affiliations: *** IBB - CNR ***
Dipartimento di Biologia Strutturale e Funzionale, UniversitÀdi Napoli Federico II, via Cinthia, 80126 Napoli, Italy
CEINGE Biotecnologie Avanzate, Napoli, Italy
Dipartimento di Chimica Organica e Biochimica, UniversitÀ di Napoli Federico II, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy
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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 IgG(1), 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 here: EDIAs bind to a different ErbB2 epitope than Herceptin and the other human/humanized antibodies against ErbB2 reported so far. The epitope has been successfully located in region 122-195 of extracellular domain I. These findings could lead to the identification of novel epitopes on ErbB2 that could be used as potential therapeutic targets to mitigate anti-ErbB2-associated cardiotoxicity and eventually overcome resistance.
A novel ErbB2 epitope targeted by human antitumor immunoagents
Cusanno F, Cisbani E, Colilli S, Fratoni R, Garibaldi F, Giuliani F, Gricia M, Lucentini M, Magliozzi ML, Santarivenere F, Torrioli S, Cinti MN, Pani R, Pellegrini R, Simonetti G, Schillaci O, Del Vecchio S, Salvatore M, Majewski S, De Vincentis G, Scopinaro F * Results of clinical trials with SPEM(278 views) Nucl Instrum Methods Phys Res Sect A, 2007 Feb 1; 497(1): 46-50. Impact Factor:3.221 ViewExport to BibTeXExport to EndNote