Abstract 1539: In vivo study of natural killer cell cytotoxicity against cholangiocarcinoma in a nude mouse model

Abstract

Abstract NK cell is one of the lymphocytes clinically used for various cancer types. Cytotoxicity of NK cell to cholangiocarcinoma (CC), however, has not been studied yet, nor has NK cell therapy against CC been clinically applied. In this study, relevance of NK cell therapy for antitumor efficacy against CC was preclinically investigated. Human HuCCT-1 cells, an intrahepatic CC cell line, were xenografted into nude mice. The HuCCT-1 tumor-bearing nude mice then received multiple infusions of ex vivo expanded human NK cell (SMT01) and were evaluated for in vivo cytotoxic activity of the NK cells. Dosage-dependent safety and toxicity of SMT01 was evaluated at three different dose levels. The mice well tolerated the maximum dose of SMT01. All of the three dosage groups did not show any significant adverse event. To evaluate in vivo activity of SMT01 against CC, we administered 5 infusions of SMT01 into the HuCCT-1 tumor-bearing nude mice. A standard chemotherapy as a positive control was also included. The result showed that SMT01 infusions resulted in significant inhibition of the CC tumor growth compared to the negative control (normal saline infusion), suggesting that NK cell contains in vivo cytolytic activity against cholangiocarcinoma. When body weights of the nude mice were measured, however, the body weight of the nude mice administered with chemotherapy was found to be maintained as lowest among all treatment groups while all the NK cell infusion groups well maintained the body weight during the treatment, suggesting beneficial effect of NK cell therapy in relevance of quality of life. IHC experiments and TUNEL assay using the tumor tissue sections clearly supported the cytotoxicity results of SMT01 against CC. We found that a robust infiltration of the infused NK cells was located along the loose tissue where feeding vessels entered. TUNEL-positive tumor cells were mainly localized at the vicinity of populated NK cells. In conclusion, our in vivo study demonstrates that NK cell also contains cytolytic activity against cholangiocarcinoma. Further investigation of the NK cell-based immunotherapy can be useful to determine cancer therapeutics for the specific tumor. Citation Format: Inhye Jung, DoHee Kim, Yong Yoon Chung, Seung Woo Park, Da Kyung Yoo. In vivo study of natural killer cell cytotoxicity against cholangiocarcinoma in a nude mouse model [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 1539.