Abstract CT214: High purity and activity NK cells therapy in patients with advanced gastrointestinal cancer: Phase I study
Authors: Okayama Tetsuya , Kokura Satoshi , ishikawa Takeshi , Sakamoto Naoyuki , Ideno Mitsuko , Sakai Fumiyo , Kato Akiko , Enoki Tatsuji , Mineno Junichi , Konishi Hideyuki , Naito Yuji , Itoh Yoshito , Yoshikawa Toshikazu 
Published: May 2015

Abstract
PURPOSE:
Our group exploited the novel technique of cultivating high purity and activity NK cells compared with traditional technique from peripheral blood of cancer patients. This phase I study investigated the safety and maximum-tolerated dose of the infusion NK cell number in patients with untreatable advanced gastrointestinal cancer.
PATIENTS AND METHODS:
Patients with gastrointestinal cancer who previously failed standard chemotherapy regimens were treated with three doses of NK cells infusion. We set three dose levels of NK cells infusion. The numbers of infusion NK cells were 5 X 108 cells as cohort 1, 1 X 109 cells as cohort 2, 2 X 109 cells as cohort 3 and each patient was infused NK cells three times per 1 or 2 weeks. The culture method of NK cells described as below; firstly CH296 (FN-CH296, RetroNctin®) induced T cells (RN-T) were prepared in advance by previously reported method, and processed to use as stimulator cells. NK cells were expanded from peripheral blood mononuclear cells by stimulating with modified RN-T, OK-432 and IL-2, then cultured for 21-22 days. We also established large-scale culture system using gas-permeable culture bag for clinical application.
RESULTS:
14 patients were totally enrolled in this study. Of 14 patients, 7 patients were enrolled in cohort 1 study. Of 7 patients, 4 patients couldn't complete NK cells infusion because of some reasons such as bad NK cell proliferation, less purity of active NK cells and worsening of primary cancer. 3 patients could complete in cohort 1. 4 patients were enrolled in cohort 2 study. Of 4 patients, 1 patient couldn't complete the NK cell infusion because of worsening of primary cancer. 3 patients could complete and 1 patient experienced grade 2 pleural effusion accumulation. In cohort 3 study, 3 patients were enrolled. All of 3 patients could complete NK cells infusion, and only 1 patient experienced grade 1 low grade fever. As clinical response, 1 partial response (PR) at cohort 2 and 6 stable diseases (SD) at 4 patients in cohort 1, 1 patient in cohort2 and 1 patient in cohort 3 were observed. In addition, we checked the immune monitoring in detail for all patients.
CONCLUSIONS:
High purity and activity NK cells therapy was safety and maximum-tolerated dose was 2 X 109 cells. The evaluation is needed to further refine the efficacy and the toxicity of the combination therapy, chemotherapy, IgG1 molecular target drugs and this therapy for using this therapy in clinical in the future.
Citation Format: Tetsuya Okayama, Satoshi Kokura, Takeshi ishikawa, Naoyuki Sakamoto, Mitsuko Ideno, Fumiyo Sakai, Akiko Kato, Tatsuji Enoki, Junichi Mineno, Hideyuki Konishi, Yuji Naito, Yoshito Itoh, Toshikazu Yoshikawa. High purity and activity NK cells therapy in patients with advanced gastrointestinal cancer: Phase I study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT214. doi:10.1158/1538-7445.AM2014-CT214