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Abstract C165: Discovery of a lectin-like receptor family protein as a novel target for monoclonal antibody therapy.

2013; American Association for Cancer Research; Volume: 12; Issue: 11_Supplement Linguagem: Inglês

10.1158/1535-7163.targ-13-c165

1538-8514

Susanna Campagnoli, Matteo Parri, Alberto Grandi, Elisa De Camilli, Luigi Terracciano, Boquan Jin, Giuseppe Viale, Paolo Sarmientos, Guido Grandi, Piero Pileri, Renata Grifantini,

Monoclonal and Polyclonal Antibodies Research

Abstract In our recent research activities, we identified a panel of novel candidate markers for prevalent cancers by a systematic tissue microarray analysis (TMA) of a large collection of polyclonal antibodies (approximately 1600) raised against membrane-associated and secreted human proteins currently marginally characterized. Of major interest were those proteins specifically detected in one or more of the five tumors with significant frequencies (data from 50 patients per each of the five cancers) and showing surface exposure on cancer cells. Among them, here we describe the molecular characterization of novel surface-associated protein belonging to the lectin-binding family proteins (involved in the innate immune response) for which very little knowledge exists. The protein was mainly over-expressed in breast, lung and ovary cancers (approximately 30-40% of tested cases) and it is involved in cell proliferation, migration and and invasiveness, as demonstrated by gene silencing using specific siRNA technology. Highly specific murine monoclonal antibodies (mAbs) were generated toward it are able to recognize the protein on the surface of breast and ovary cell lines. Of particular interest are two mAbs, which, upon binding, are efficiently internalized by breast and ovary cancer cells, indicating that they are amenable for the generation of antibody-drug conjugates. These two mAbs influence viability of breast and ovary cells in vitro. One of them shows antibody-dependent cell-mediated cytotoxicity in vitro on breast cancer cells. In vivo efficacy studies are ongoing to evaluate their therapeutic activity. Overall, data indicate that the lectin-binding protein and the specific mAbs here described could be developed as a novel tool for a targeted therapy alone or in combination with other treatments. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C165. Citation Format: Susanna Campagnoli, Matteo Parri, Alberto Grandi, Elisa De Camilli, Luigi Terracciano, Boquan Jin, Giuseppe Viale, Paolo Sarmientos, Guido Grandi, Piero Pileri, Renata Maria Grifantini. Discovery of a lectin-like receptor family protein as a novel target for monoclonal antibody therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C165.