P53.04 KUgliptin, a Novel and Potent DPP4 Inhibitor, Improves of Combined Therapy with Immune Checkpoint Inhibitor (ICI) in Lung Cancer Immunotherapy

Abstract

Lung cancer is the most common cause of death rate among all cancer related diseases. Although several drugs including immunotherapeutics (Immune checkpoint inhibitor; ICI) have been developed and used in recent years, the response rate is limited to about 25%. Therefore, many researchers have tried to combine treatment with other drugs to increase the therapeutic efficiency of ICI. Dipeptidyl peptidase 4 (DPP4) is a ubiquitously expressed transmembrane exopeptidase on the cell surface of many hematopoietic cells. According to some reports, DPP4 inhibitors have the ability to suppress tumor proliferation and tumor metastasis. KUgt-123, is a novel and potent DPP4 inhibitor, it is chemical structural based in adamantane structure modified. This study was performed to combined treatment of KUgt-123 for improvement of therapeutic efficacy of immune checkpoint inhibitor for lung cancer. To confirm the cytotoxicity effect of KUgt-123, it was dose dependently treated in human lung carcinoma epithelial cell line (A549) and mouse Lewis lung carcinoma (LLC) cells then using MTT assay. PD-L1 expression level was determined by western blot analysis. TC-1 tumor-bearing mice were treated with either PD-1 antibody treatment group and/or KUgt-123 treatment. KUgt-123 was shown to inhibit the cell proliferation in A549 cells and LLC cells. The result that cell growth was reduced dose dependently of KUgt-123. PD-L1 expression was reduced by KUgt-123 treatment in TC-1 cells. TC-1 tumor bearing C57BL/6 mice, the size of tumors was reduced by alone KUgt-123 treatment and significantly reduced co-treatment with mouse PD-1 antibody. Our data provide evidence that KUgt-123 might be a good co-treatment reagent for improves the efficacy of ICI in lung cancer treatment.