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      Drug Design, Development and Therapy (submit here)

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      Adjuvant immunotherapy of dendritic cells and cytokine-induced killer cells is safe and enhances chemotherapy efficacy for multiple myeloma in China: a meta-analysis of clinical trials

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          Abstract

          Objective

          The aim of this study was to systematically evaluate the efficacy and safety of the combination of dendritic cells and cytokine-induced killer cells (DC–CIK) adjuvant immunotherapy and chemotherapy in the treatment of multiple myeloma (MM).

          Methods

          Clinical trials were gathered by searching Web of Science, PubMed, Embase, Cochrane Library, Wanfang, and CNKI database. Outcome measurements including therapeutic efficacy, prognosis, immune function, and adverse events were extracted and evaluated.

          Results

          A total of 12 trials including 594 MM patients were involved in this study for statistical analysis. Results indicated that compared to chemotherapy alone, the combination of DC–CIK immunotherapy with chemotherapy significantly improved patients’ overall response rate (ORR, odds ratio [OR] =2.77, 95% confidence interval [CI] =1.88–4.10, P<0.00001), disease control rate (DCR, OR =2.90, CI =1.72–4.90, P<0.0001), and life quality ( P<0.00001). The combined therapy showed advantages over chemotherapy alone in prognostic indicators including percentage of tumor cells ( P=0.04), serum levels of β2-microglobin ( P<0.0001), M protein ( P<0.00001), and creatinine ( P<0.0001), and 24 h urine light chains ( P<0.00001). After combined treatment, CD4 + lymphocyte subsets’ percentages, CD4 +/CD8 + ratio, and cytokines levels of AgNOR, IFN-γ, IL-2, and IL-12 were significantly increased ( P<0.05), whereas CD8 + and CD4 +CD25 + percentages and IL-4, IL-6, IL-10, and TGF-β levels were obviously decreased ( P<0.01), indicating a recovered immune condition.

          Conclusion

          Adjuvant DC–CIK immunotherapy enhances the efficacy of chemotherapy for MM and improves prognosis probably by reconstructing immune function.

          Most cited references44

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma.

            No adjuvant therapy has been shown to extend the survival of patients with hepatocellular carcinoma (HCC) receiving curative treatment. We investigated whether injections of activated cytokine-induced killer (CIK) cells (CD3+/CD56+ and CD3+/CD56- T cells and CD3-/CD56+ natural killer cells) prolongs recurrence-free survival of patients after curative therapy for HCC.
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              Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy

              Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3+CD56+ natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor. Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                15 November 2017
                : 11
                : 3245-3256
                Affiliations
                [1 ]Department of Clinical Laboratory
                [2 ]Department of Blood Transfusion
                [3 ]Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China
                Author notes
                Correspondence: Hong Liu; Anqi Zhang, Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Dongchang West Road, No 67, Liaocheng 252000, Shandong Province, China, Tel +86 130 3453 4783; +86 158 0635 8395, Email liuh4783@ 123456126.com ; zhang_angela1119@ 123456163.com
                Article
                dddt-11-3245
                10.2147/DDDT.S146959
                5695269
                1a8a9430-48b8-4cf7-a1f6-e1624b0fdf70
                © 2017 Wang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                cytokine-induced killer cells,dendritic cells,multiple myeloma,adjuvant immu-notherapy,meta-analysis

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