Abstract 4622: Discovery of a novel target for monoclonal antibody therapy of breast and ovary cancers
2014; American Association for Cancer Research; Volume: 74; Issue: 19_Supplement Linguagem: Inglês
10.1158/1538-7445.am2014-4622
ISSN1538-7445
AutoresAlberto Grandi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Boquan Jin, Paolo Sarmientos, Guido Grandi, Luigi Terracciano, Giuseppe Viale, Piero Pileri, Renata Grifantini,
Tópico(s)Glycosylation and Glycoproteins Research
ResumoAbstract In our recent research activities, we identified a panel of novel candidate markers for prevalent cancers by a systematic immune-histochemical screening with a large collection of polyclonal antibodies (approximately 1600) raised against membrane-associated and secreted human proteins currently marginally characterized. Of utmost interest were those proteins over-expressed detected in one or more tumors showing surface exposure on cancer cells. Among them, here we describe the molecular characterization of a novel surface-associated protein (EXN36) belonging to the lectin-binding protein family for which very little is presently known. We found that the protein is mainly over-expressed in breast and ovary cancers (frequency of approximately 30-40% of tested cases, based on analysis of 50 patients) and it is involved in cell proliferation, migration and invasiveness, as demonstrated by gene silencing. With the intent of exploiting EXN36 as therapeutic target for monoclonal antibody (mAb) therapy, highly specific murine mAbs were generated and proved to recognize the protein on the surface of selected breast and ovary cell lines. Of particular interest are two mAbs, which, upon binding, are efficiently internalized by breast and ovary cancer cells. These two mAbs influence the viability of breast and ovary cells in vitro. One of them shows antibody-dependent cell-mediated cytotoxicity in vitro in breast cancer cells. An analysis of their biodistribution in normal human tissues showed that these mAbs have limited cytoplasmic reactivity in some tissues. Overall, the functional properties of the anti-EXN36 mAbs make them amenable for the generation of antibody-drug conjugates (ADCs). Moreover, they could be exploited for immune-nanoparticles targeted delivery systems. In vivo efficacy in breast and ovary xenograft cancer models are ongoing to evaluate their therapeutic activity either as naked antibodies or ADCs. Overall, data indicate that EXN36 and the specific mAbs represent innovative and promising tools for a targeted mAb therapy of breast and colon cancer, either alone or in combinatorial therapeutic strategies. Citation Format: Alberto Grandi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Boquan Jin, Paolo Sarmientos, Guido Grandi, Luigi Terracciano, Giuseppe Viale, Piero Pileri, Renata Maria Grifantini. Discovery of a novel target for monoclonal antibody therapy of breast and ovary cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4622. doi:10.1158/1538-7445.AM2014-4622
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