Zhen Zhang1, Xianlan Zhao2, Tengfei Zhang1, Liping Wang3, Lingzhu Yang2, Lan Huang4, Feng Li4, Jinyan Liu5, Dongli Yue1, Fei Wang5, Jieyao Li1, Fangxia Guan6, Yuming Xu7, Bin Zhang8, Yi Zhang9. 1. Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 2. Department of Obstetrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 3. Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 4. Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 5. Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; School of Life Science, Zhengzhou University, Zhengzhou, Henan, China. 6. School of Life Science, Zhengzhou University, Zhengzhou, Henan, China. 7. Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 8. Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, Illinois, USA. 9. Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; School of Life Science, Zhengzhou University, Zhengzhou, Henan, China; Key Laboratory of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: yizhang@zzu.edu.cn.
Abstract
BACKGROUND AIMS: Cytokine-induced killer (CIK) cell therapy represents a feasible immunotherapeutic option for treating malignancies. However, the number of anti-tumor lymphocytes cannot be easily obtained from the cancer patients with poor immunity status, and older patients cannot tolerate repeated collection of blood. Cord blood-derived CIK (CB-CIK) cells have shown efficacy in treating the patients with cancer in several clinical trials. This study was conducted to evaluate the biological characteristics and anti-tumor function of CB-CIK cells. METHODS: The immunogenicity, chemokine receptors and proliferation of CB-CIK cells were analyzed by flow cytometry. The CIK cells on day 13 were treated with cisplatin and the anti-apoptosis capacity was analyzed. The function of CB-CIK cells against the human cancer was evaluated both in vitro and in vivo. RESULTS: Compared with peripheral blood-derived CIK (PB-CIK) cells, CB-CIK cells demonstrated lower immunogenicity and increased proliferation rates. CB-CIK cells also had a higher percentage of main functional fraction CD3(+)CD56(+). The anti-apoptosis ability of CB-CIK cells after treatment with cisplatin was higher than that of PB-CIK cells. Furthermore, CB-CIK cells were effective for secreting interleukin-2 and interferon-γ and a higher percentage of chemokine receptors CCR6 and CCR7. In addition, tumor growth was greatly inhibited by CB-CIK treatment in a nude mouse xenograft model. CONCLUSIONS: CB-CIK cells exhibit more efficient anti-tumor activity in in vitro analysis and in the preclinical model and may serve as a potential therapeutic approach for the treatment of cancer.
BACKGROUND AIMS: Cytokine-induced killer (CIK) cell therapy represents a feasible immunotherapeutic option for treating malignancies. However, the number of anti-tumor lymphocytes cannot be easily obtained from the cancerpatients with poor immunity status, and older patients cannot tolerate repeated collection of blood. Cord blood-derived CIK (CB-CIK) cells have shown efficacy in treating the patients with cancer in several clinical trials. This study was conducted to evaluate the biological characteristics and anti-tumor function of CB-CIK cells. METHODS: The immunogenicity, chemokine receptors and proliferation of CB-CIK cells were analyzed by flow cytometry. The CIK cells on day 13 were treated with cisplatin and the anti-apoptosis capacity was analyzed. The function of CB-CIK cells against the humancancer was evaluated both in vitro and in vivo. RESULTS: Compared with peripheral blood-derived CIK (PB-CIK) cells, CB-CIK cells demonstrated lower immunogenicity and increased proliferation rates. CB-CIK cells also had a higher percentage of main functional fraction CD3(+)CD56(+). The anti-apoptosis ability of CB-CIK cells after treatment with cisplatin was higher than that of PB-CIK cells. Furthermore, CB-CIK cells were effective for secreting interleukin-2 and interferon-γ and a higher percentage of chemokine receptors CCR6 and CCR7. In addition, tumor growth was greatly inhibited by CB-CIK treatment in a nude mouse xenograft model. CONCLUSIONS:CB-CIK cells exhibit more efficient anti-tumor activity in in vitro analysis and in the preclinical model and may serve as a potential therapeutic approach for the treatment of cancer.