Abstract 2857: Monoclonal antibodies against novel tumor markers for cancer diagnosis and treatment .
Authors: Renata Maria Grifantini, Piero Pileri, Matteo Parri, Alberto Grandi, Susanna Campagnoli, Renzo Nogarotto, Elena De Camilli, Serenella Eppenberger, Luigi Terracciano, Giuseppe Viale, Guido Grandi, Paolo Sarmientos
Journal: Cancer Research (2013)

Abstract In our recent research activities, we identified a group of novel candidate tumor markers for prevalent cancers. Tissue microarray (TMA) representing breast, lung colon ovary and prostate cancers were analyzed by a high-throughput immunohistochemistry screening using of a library of 1600 mouse antibodies raised against membrane-associated and secreted human proteins for which little is known in the scientific literature. 89 proteins were found over-expressed in one or more of the five tumors under analysis. IHC analysis on TMA representing tissues from 50 patients per each of the five cancers allowed to select a group of 20 potential markers over-expressed in cancer with frequencies ranging from 20 to 96%, with concomitant marginal expression in normal tissues. With the aim at validating these proteins as novel markers for patient stratification, prognosis and response to therapy, highly specific monoclonal antibodies (mAbs) have been generated against them. Currently, mAbs against 4 markers able to selectively detect their target proteins in cancers by IHC have been already identified (positivity ranging from 15 up to 94%, and showing membranous or intracellular staining). The target proteins of these mAbs include:1) a scavenger receptor protein; 2) a putative metallo-protease, 3) a lectin-binding protein involved in the innate immune response, 4) a cadherin- homologous protein. The mAb clinical value is being examines using high-density TMA representing patients with known history and follow-up for breast (1553 patients), colon (1420 patients), lung (1527 patients), ovary (112 patients) and prostate (553 patients) cancers have been generated. The patient cohorts have been collected at the biobank of the institute for Pathology of Basel to select pools of prognostic/predictive monoclonal antibodies capable of discriminating i) patients with favorable or adverse prognosis, and ii) patients that respond/do not respond to specific therapeutic interventions. Available data indicated that these antibodies, alone and in combinations, show significant association with specific clinical features (formation of metastasis, progression-free survival, survival time). Interesting, some of available antibodies show therapeutic activity in preclinical cancer models. These antibodies are able to bind the surface of cancer cells in vitro and in vivo. Avalable data show that one mAb targeting the cadherin-like protein inhibits tumor growth in athymic nude mice bearing HCT15 and HT29 colon cancer xenograft models. Overall, these novel markers and their specific monoclonal antibodies could offer new opportunities for cancer diagnosis and treatment. Citation Format: Renata Maria Grifantini, Piero Pileri, Matteo Parri, Alberto Grandi, Susanna Campagnoli, Renzo Nogarotto, Elena De Camilli, Serenella Eppenberger, Luigi Terracciano, Giuseppe Viale, Guido Grandi, Paolo Sarmientos. Monoclonal antibodies against novel tumor markers for cancer diagnosis and treatment . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2857. doi:10.1158/1538-7445.AM2013-2857