Preparation of highly activated natural killer cells for advanced lung cancer therapy

Silun Xie,1 Zhenyi Wu,1 Lizhi Niu,2 Jibing Chen,3 Yunkun Ma,1 Mingjie Zhang11Research and Development Department, HANK Bioengineering Co.,Ltd, Shenzhen, People’s Republic of China; 2Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou, People’s Republic of China; 3Department of Central Laboratory, Fuda Cancer Hospital, Jinan University, Guangzhou, People’s Republic of ChinaBackground: Natural killer (NK) cells can be used as an adoptive immunotherapy to treat cancer patients.Purpose: In this study, we evaluated the efficacy of highly activated NK (HANK) cell immunotherapy in patients with advanced lung cancer.Patients and methods: Between March 2016 and September 2017, we enrolled 13 patients who met the enrollment criteria. Donor peripheral blood monocytes were isolated from patients and the NK cells were expanded. After 12 days of culture, the cells were collected and infused intravenously on days 13 to 15. The enrolled patients received at least one course including three times of infusions. The lymphocyte subsets, cytokine production, and the expression of carcinoembryonic antigen (CEA) and thymidine kinase 1 (TK1) were measured before treatment and after the last infusion.Results: No side effects were observed. After a three-month follow-up, the percentage of patients who achieved stable disease and progressive disease was 84.6% and 15.4%. Moreover, the level of IFN-γ was significantly higher after treatment and the level of CEA decreased substantially. The overall immune function of the patients who received the NK cell therapy remained stable.Conclusion: This is the first study to describe the efficacy of NK cell therapy of patients with advanced lung cancer. These clinical observations demonstrated that NK cell is safe and efficient for advanced lung cancer therapy.Keywords: adoptive immunotherapy, highly activated natural killer cells, immune function, lung cancer