Cytokine-induced killer cells in the treatment of patients with solid carcinomas: a systematic review and pooled analysis

Ma, Yue; Zhang, Zan; Tang, Lei; Xu, Yingchun; Xie, Zhi-Ming; Gu, Xiaofeng; Wang, Hongxia

doi:10.3109/14653249.2011.649185

Cited by 63 publications

(42 citation statements)

References 30 publications

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“…3,[22][23][24][25][26] Several reviews and meta-analysis reports have also demonstrated the safety and effectiveness of adjuvant CIT in clinics. [27][28][29][30] However, the patterns of CIT require thorough investigation in order to achieve optimal outcome and cost-effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

et al. 2015

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Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 y old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with alternate application of CIK and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients 60 y old with positive lymph nodes.

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Section: Introductionmentioning

confidence: 99%

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

et al. 2015

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“…There was prolongation of recurrence-free survival but no improvement of overall survival (OS) [130]. Immunotherapy using CIK cells significantly improved both OS and progression-free survival of HCC patients, although further study through a large-scale, multi-center, randomized clinical trial should be conducted [131][132]. A preliminary report about an alternative TIL approach also showed encouraging outcomes.…”

Section: Immunotherapy Against Hcv-and Hbv-associated Tumorsmentioning

confidence: 89%

“…To date, clinical trials have evaluated transfer of several different immune effector cells for the treatment of HCC, including IL-2-and anti-CD3-activated autologous PBMCs [130], cytokine-induced killer (CIK) cells [131][132], NK and NKT cells (NCT02008929 and NCT01801852), and TILs (NCT01462903). Takayama et al reported 76/150 patients who had undergone curative resection of HCC received adjuvant autologous lymphocyte infusions.…”

Section: Immunotherapy Against Hcv-and Hbv-associated Tumorsmentioning

confidence: 99%

Immunotherapy against cancer-related viruses

2016

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Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects.

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“…[12][13][14][15] Ex vivo and in vivo experimental evidence has demonstrated that cytokineinduced killer (CIK) cells generated with a "cytokine cocktail" 16,17 result in CIK cells with a high level of cytotoxic activity in a broad range of tumor cell lines, supporting their use for adoptive immunotherapy and have yielded encouraging results. [18][19][20] It is hypothesized that the tumorspecific cellular components of CIK therapy may be responsible for the clinical benefits observed in some cancer patients who receive this therapy. 21 Co-culture of CIK with cytokine producing DCs has elicited an increase in the antitumor activity of CIK cells.…”

Section: Introductionmentioning

confidence: 99%

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

et al. 2016

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Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophagecolony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy.Patients and Methods: We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy.Results: Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR b sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients.Conclusions: Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

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Cytokine-induced killer cells in the treatment of patients with solid carcinomas: a systematic review and pooled analysis

Cited by 63 publications

References 30 publications

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

Immunotherapy against cancer-related viruses

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

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