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      Human leukocyte antigen-haploidentical donor-derived cytokine-induced killer cells are safe and prolong the survival of patients with advanced non-small cell lung cancer

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          Abstract

          The aim of the present study was to evaluate the safety and efficacy of administering cytokine-induced killer cells (termed allogeneic CIKs), obtained from the blood of the offspring of patients, for the treatment of non-small cell lung cancer. Symptoms, signs and laboratory assessment results for 303 cancer patients were collected prior to and following treatment with autologous or allogeneic CIKs. In addition, 54 patients with advanced non-small cell lung cancer (NSCLC) were enrolled and divided into allogeneic CIK and optimal support groups (n=27 per group) according to gender, age, Karnofsky performance status score, TNM stage and histological type. In addition, overall survival (OS) was compared between the two groups. A total of 303 patients were treated with CIKs for 647 cycles, with 308 and 339 cycles in the autologous and allogeneic CIK groups, respectively. The mean number of CIKs in the autologous and allogeneic groups was 2.11±0.32×10 10 and 2.29±0.36×10 10, respectively, with no marked differences identified between the two groups (t=1.147; P>0.05). The predominant adverse events included insomnia, fever, nausea, vomiting and mild abdominal pain, which were found, respectively, in nine (6.8%), eight (6.0%), two (1.5%) and one (0.8%) patients receiving autologous CIKs and 11 (6.5%), 10 (5.9%), one (0.6%) and one (0.6%) patients receiving allogeneic CIKs, with no marked differences identified between the two groups (P>0.05). Adverse events were not associated with cell count, frequency or duration of treatment. Following CIK treatment, the outcomes of routine blood tests, and liver and kidney function tests, as well as immune function and electrocardiogram examinations remained unchanged (P>0.05). The median OS was 11.0 months (95% confidence interval (CI), 8.6–13.4 months) and 8.0 months (95% CI, 5.3–10.7 months) for NSCLC patients receiving allogeneic CIKs and optimal support, respectively; a statistically significant difference was identified (χ 2=5.618; P=0.018). The present study demonstrated that CIKs from human leukocyte antigen haploidentical donors are safe and prolong the survival of NSCLC patients.

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          The new lung cancer staging system.

          The International Association for the Study of Lung Cancer (IASLC) has conducted an extensive initiative to inform the revision of the lung cancer staging system. This involved development of an international database along with extensive analysis of a large population of patients and their prognoses. This article reviews the recommendations of the IASLC International Staging Committee for the definitions for the TNM descriptors and the stage grouping in the new non-small cell lung cancer staging system.
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              Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC).

              Recently, a subset of natural killer T lymphocytes termed "cytokine-induced killer (CIK) cells" has been described. To build an international registry, we collected the clinical data and treatment of patients with cancer using CIK cells from the literature and the respective investigators. This registry is expected to set a new set of standards on the reporting of results from clinical trials using CIK cells. A standardized reporting system will accelerate discoveries and allows us to improve treatment to benefit the patients. We searched in PubMed for "CIK cells clinical trials". Within the 867 matches found, 11 clinical trials with CIK cells were identified. Within these trials, 426 patients were treated, of which 313 were male, and 113 were female. Most trials included male patients with hepatocellular carcinoma, gastric cancer, and Hodgkin or non-Hodgkin disease. In 10 of 11 studies, autologous CIK cells were used. The total number of CIK cells injected ranged from 21.9 × 10(7) to 5.2 × 10(10). The number of CIK cells used per infusion ranged from 7.2 × 10(6) to 2.1 × 10(10). Patients were treated with up to 40 infusions of CIK cells. Of the 384 patients, where a clinical response was reported, 24 patients showed a complete response, 27 patients showed a partial response, 40 patients showed a minor response. The total response rate (RR) was 91/384 reported patients, 161 patients had a stable disease, 129 patients had progressive disease. A decrease in tumor volume was only described in three patients. Side effects of CIK cell treatment were minor. Interestingly, a reduction of hepatitis B virus load was described in patients undergoing treatment with CIK cells. Disease-free survival rates were significantly higher in patients treated with CIK cells than in a control group without CIK treatment. Adjuvant immunotherapy with cytokine-induced killer cells may prevent recurrence and improve quality of life and progression-free survival rates in patients with cancer.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                December 2014
                24 September 2014
                24 September 2014
                : 8
                : 6
                : 2727-2733
                Affiliations
                Department of Biotherapy and Laboratory of Biotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China
                Author notes
                Correspondence to: Professor Shiyong Wang, Department of Biotherapy and Laboratory of Biotherapy, The Fourth Affiliated Hospital of China Medical University, 4 East Chongshan Road, Shenyang, Liaoning 110032, P.R. China, E-mail: sywang66@ 123456yahoo.com
                Article
                ol-08-06-2727
                10.3892/ol.2014.2558
                4214449
                fbf94d2e-b0a1-4c3b-b210-10079f5420f4
                Copyright © 2014, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 12 July 2013
                : 23 January 2014
                Categories
                Articles

                Oncology & Radiotherapy
                cytokine-induced killer cells,immunotherapy,adoptive,allogeneic,malignant tumor,carcinoma,non-small cell lung

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