Abstract
Abstract Most targeted therapy drugs block the growth of cancer cells by targeting specific molecules needed for tumor growth. Among targeted therapy drugs, cetuximab, the monoclonal antibody which binds to epidermal growth factor receptor (EGFR) and inhibits downstream signaling of EGFR, has greatly improved the median survival of patients with metastatic colorectal cancer (CRC). Yet, cetuximab showed limited therapeutic effect in CRC patients who carry certain mutation in the KRAS, which emphasizes the necessity of developing new targeted therapy drugs for CRC. KIA1114 is a full-length protein of the trophinin gene and is localized on the cell surface. In our previous research, we identified the role of KIA1114 as a novel surface marker of tumor initiating cells of hepatocellular carcinoma (HCC) by developing Kiatomab, KIA1114-specific monoclonal antibody. Here, we show that KIA1114 is also highly expressed in various CRC cells with mouse or human origin. Kiatomab treatment inhibits tumor growth in a syngeneic graft CRC mouse model in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) dependent manner. In the metastatic CRC model, Kiatomab therapy suppresses metastasis, with a significant increase of survival. Of note, the anticancer efficacy of Kiatomab is further improved by combinatorial treatment with the standard chemotherapeutic agent cyclophosphamide (CTX), in both metastatic and solid tumor models. In summary, our findings suggest that KIAA1114 is a new target for CRC and its monoclonal antibody Kiatomab might have a potential for anticancer therapy. Citation Format: Young Min Kim, Sae Won Kim, Seungwon Lee, Hyekang Kim, Ji-Hae Kim, Han Wook Park, Young Chul Sung, Seung-Woo Lee. Preclinical study of Kiatomab, a novel monoclonal antibody to the cancer stem cell surface marker KIAA1114, for anti-cancer therapy in colorectal carcinoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B012.
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