Abstract 2909: Development of new mechanism based therapeutic antibodies in non-small cell lung cancer

Abstract

Abstract Lung cancer is second most common cancer in the world. Non Small Cell Lung Cancer (NSCLC) accounts approximately 80-85% of all lung cancer diagnosis. Traditional therapies of this disease were surgical resection, chemotherapy, and radiotherapy, alone or in combination. In addition, targeted therapeutic approach was based on the concept of discovering genetic alterations and the signaling pathways in cancer. Recently, to overcome the critical points for standard therapies, many groups were studied immunotherapeutic approaches, such as programed cell-death protein 1 (PD-1) antibody. However, rational use of these agents has been limited by the lack of a definitive predictive biomarker. Therefore, we identified new target, cancer immunotherapy related gene, CMG by shRNA libraries screening analysis on chemo-agents & target therapy resistant non-small cell lung cancer cells. First of all, we investigated CMG expression by immunohistochemistry in various tissue microarray (TMA). These results show that CMG highly expressed in Lung cancer, Liver cancer, and gastric cancer. We investigated target potentials on lung cancer, liver cancer, and gastric cancer cell lines using in vitro and in vivo assay system. Knockdown of CMG by CMG shRNA was induced cell death in various cancer cell lines. In addition, suppression of CMG was induced tumor size regression in CMG shRNA stable cell lines-derived xenograft model. Based on these results, we synthesized a novel series of CMG therapeutic antibody. CMG therapeutic antibody is a lead antibody for treating Lung cancer patients who express CMG gene. These antibodies have anti-cancer effects and immunotherapeutic effects in lung cancer (NSCLC), liver cancer, and gastric cancer. In addition, the in vivo efficacy of CMG antibody was assessed in mouse lung cancer derived syngeneic mouse model. The CMG antibody was tri-daily i.p. injected and the tumor volume was measured and compared between groups. Dramatic tumor regression was observed in CMG antibody treated group. These results were shown that these antibodies have immunotherapeutic potentials. In conclusion, CMG is a promising target for Lung cancer patients (chemo-agents resistant or PD-1 resistant Lung cancer patienrts). Our antibodies can be promising therapeutic agents for lung cancer, Liver cancer, and gastric cancer. Citation Format: Jai-hee Moon, Dae Hee Lee, Jae-Sik Shin, Joseph Kim, Yoon Sun Park, Seung-Woo Hong, So Hee Lee, Mi Jin Kim, Joonyee Jung, Chun-Ho Park, Sun-Chul Hur, Hyojin Kim, Hyebin Park, Sang Soo Park, Jun Ki Hong, Ji Hee Gong, Jieun Kim, Hyun Ho Lee, Il-Whea Ku, Dong-Hoon Jin. Development of new mechanism based therapeutic antibodies in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2909.