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Abstract C190: A novel monoclonal antibody for colon cancer therapy.

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

10.1158/1535-7163.targ-13-c190

1538-8514

Alberto Grandi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Ilaria Naldi, Lisa Gherardini, Caterina Cinti, Luigi Terracciano, Boquan Jin, Paolo Sarmientos, Giuseppe Viale, Guido Grandi, Piero Pileri, Renata Grifantini,

Glycosylation and Glycoproteins Research

Abstract In our recent research activities, we identified 89 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. Monoclonal antibodies were generated towards 20 distinct antigens that are being characterized and validated for diagnostic and therapeutic applications. Here we describe a monoclonal antibody (mAb) targeting a protein of the protocadherin- family in colo-rectal cancer (CRC). The antibody specifically recognizes its target protein in cancer tissues, with concomitant negligible or marginal reactivity in normal colon. The protein was not previously described as CRC target. IHC data from CRC samples of approximately 200 patients, (collected at the bio-bank of the institute for Pathology of Basel, Switzerland and at the European Institute of Pathology of Milan, Italy) showed that the antibody binds up to 80% CRC cases (stages from 1 to 4) with high or moderate intensity. In most cases, the antibody gives plasma membrane by Immune Histochemistry (IHC). An expanded analysis on approximately 1000 CRC cases is ongoing to assess whether the membranous IHC staining associates with specific clinic-pathological parameters. IHC analysis of 35 normal human tissues revealed that it gives intracellular staining in skeletal muscle, pituitary glands and prostate, whereas it gives background irrelevant staining in the other 32 tissues. The antibody is able to bind the surface of different colon cancer cells in vitro and in vivo. Upon binding it is efficiently internalized by colon cancer cells, suggesting that it can be exploited for the development of Antibody-Drug-Conjugate (ADC). Moreover, it inhibits tumor growth in athymic nude mice bearing HCT15 and HT29 colon cancer xenografts. Overall, data indicate that this monoclonal antibody could be developed for a targeted therapy of colo-rectal cancers, alone or in combinatorial strategies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C190. Citation Format: Alberto Grandi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Ilaria Naldi, Lisa Gherardini, Caterina Cinti, Luigi Terracciano, Boquan Jin, Paolo Sarmientos, Giuseppe Viale, Guido Grandi, Piero Pileri, Renata Maria Grifantini. A novel monoclonal antibody for colon cancer 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 C190.