Abstract 4458: New HDAC inhibitor (M166) has a synergistic effect with immune checkpoint inhibitor in lung cancer treatment

Recently, Immune checkpoint inhibitor (ICI) has been widely applied to various types of cancer therapies and it is used as a treatment in clinical application. ICI has a higher effect on lung cancer than other cancers; however, the treatment efficiency is only about 25%. Therefore, many research groups are making efforts to improve treatment efficiency with co-treatment therapy using chemical medications and ICIs. We evaluated the efficacy of a new PAN-HDAC inhibitor (M166) and ICI. M166 showed growth inhibition in mouse lung cancer cell (TC-1) line, mouse lung carcinoma (LLC) and human lung cancer cell (A549) line compared with normal epithelial cell lines (NIH3T3 and HEK293. Also, we checked ten kinds of immune-related cytokines and chemokines in mRNA level by treated with M166 using RT-PCR methods. CCL2 and CXCL10 chemokines are significantly increased by dose-dependently. These results indicate that M166 regulates immune response by CCL2 and CXCL10 chemokine related pathways. In order to check the synergistic effect of ICI plus HDACi co-treatment, we explored the employment of M166 in combination with ICI in a preclinical mouse model. For in vivo experiment, the mice were divided into four groups: group 1 received no treatment after the E7-expressing TC-1 tumor challenge, group 2 was treated with M166, group 3 was treated with mouse PD-1 antibody, and group 4 was both treated with M166 and mouse PD-1 antibody. The combination therapy of M166 and mouse PD-1 antibody significantly inhibited tumor growth. These results indicate that ICI plus HDACi treatment induces tumor growth inhibition through an immune response. These findings have important implications for future clinical translation. Citation Format: Sung Yong Lee, Hyun-Seock Shin, Juwhan Choi. New HDAC inhibitor (M166) has a synergistic effect with immune checkpoint inhibitor in lung cancer treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4458.