Yuanlong Gu1, Huimin Lv2, Juan Zhao2, Qi Li2, Guannan Mu2, Jiade Li2, Jiazi Wuyang2, Ge Lou3, Ruitao Wang4, Yanqiao Zhang5, Xiaoyi Huang6. 1. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China. 2. Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150081, China. 3. Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin 150081, China. 4. Department of Internal medicine, Harbin Medical University Cancer Hospital, Harbin 150081, China. 5. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China. Electronic address: yanqiaozhang@ems.hrbmu.edu.cn. 6. Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150081, China; Center of Translational Medicine, Harbin Medical University, Harbin 150086, China. Electronic address: xyhuang@hrbmu.edu.cn.
Abstract
OBJECTIVE: Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. RESULTS: After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACT<4cycles subgroup (P=0.0316). The percentage of CIK cells in patients who received ≥4cycles of ACT was higher than that in patients treated with <4cycles of ACT (P=0.0376). Notably, CIK cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. CONCLUSIONS: Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC.
OBJECTIVE: Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. RESULTS: After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACT<4cycles subgroup (P=0.0316). The percentage of CIK cells in patients who received ≥4cycles of ACT was higher than that in patients treated with <4cycles of ACT (P=0.0376). Notably, CIK cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. CONCLUSIONS: Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC.
Authors: Yutao Li; Amit Sharma; Xiaolong Wu; Hans Weiher; Dirk Skowasch; Markus Essler; Ingo G H Schmidt-Wolf Journal: Front Oncol Date: 2022-05-11 Impact factor: 5.738