Cytokine-induced killer (CIK) cell therapy for patients with hepatocellular carcinoma: efficacy and safety

Ma, Yue; Xu, Yingchun; Tang, Lei; Zhang, Zan; Wang, Jian; Wang, Hongxia

doi:10.1186/2162-3619-1-11

Cited by 75 publications

(47 citation statements)

References 24 publications

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“…22 However, these studies were not RCT, and the study populations were heterogeneous and the sample sizes were relatively small. 21,23 The present trial was conducted to better evaluate the role of CIK as an adjuvant therapy after curative resection for HCC.…”

Section: Discussionmentioning

confidence: 99%

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Xu¹,

Wang²,

Kim

et al. 2015

OncoImmunology

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Background & Aims: There is no generally accepted adjuvant therapy for hepatocellular carcinoma (HCC) after curative resection. Autologous cytokine-induced killer (CIK) cells therapy has been reported to improve outcomes of patients with HCC, but its role as an adjuvant therapy remains unclear. This study aimed to evaluate the efficacy and safety of CIK as an adjuvant therapy for HCC after curative resection.Methods: This is a single center, phase 3, open label, randomized controlled trial (RCT). Two hundred patients who were initially diagnosed with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A or B, and underwent curative hepatectomy were randomly assigned to receive four cycles of CIK treatment (the CIK group, n D 100) or no treatment (the control group, n D 100). The primary outcome was time to recurrence. The secondary outcomes included disease-free survival (DFS), overall survival (OS) and adverse events.Results: All patients in the CIK group finished the treatment by protocol. The median time to recurrence (TTR) was 13.6 (IQR 6.5-25.2) mo in the CIK group and 7.8 (IQR 2.7-17.0) mo in the control group (p D 0.01). There were no significant differences between the groups in DFS and OS. All adverse events were grade 1 or 2. There were no significant differences in incidence between the two groups.Conclusions: Four cycles of CIK therapy were safe and effective to prolong the median TTR in patients with HCC after curative resection, but the treatment did not improve the DFS and OS.

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Section: Discussionmentioning

confidence: 99%

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Xu¹,

Wang²,

Kim

et al. 2015

OncoImmunology

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“…DCs are currently considered the most powerful antigen-presenting cells in the body; they effectively present tumor antigens to T lymphocytes and function as a bridge between the tumor cells and T cells (7,19). CIK cells exhibit strong antitumor activity and non-major histocompatibility complex-restricted tumor-killing characteristics (10,20). A number of studies suggest that CIK cells co-cultured with DCs exhibit stronger tumoricidal effects and have already produced better results in different tumor types (21,22).…”

Section: Discussionmentioning

confidence: 99%

Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine-induced killer cell therapy in hepatobiliary and pancreatic cancer

Zhang

Zhu

et al. 2015

Molecular and Clinical Oncology

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Abstract. The aim of this study was to determine the therapeutic effects of adoptive immunotherapy following dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy and evaluate its cytotoxicity, survival benefits and quality of life (QOL) changes in patients with hepatobiliary and pancreatic cancer (HPC). We performed a retrospective analysis of 407 clinical cases, including 77 patients with HPC who received immunotherapy with DC vaccine and CIK cells (I group) and 330 patients with similar characteristics who underwent baseline treatment but did not receive immunotherapy [non-immunotherapy (NI) group)] as the control group. After a follow-up period of 294±207.5 days, the median survival time (MST) of the two groups was compared using the Kaplan-Meier method. In the I group, 61% of the patients developed a positive, delayed-type hypersensitivity response and 65% of the patients exhibited an improvement in QOL. The most notable adverse events included fever (28%), insomnia (25%), anorexia (17%), skin rash (12%) and arthralgia (31%). No severe toxicities were observed in patients in the I group; in addition, the MST was significantly longer in the I group compared with that in the NI group (P=0.014). Thus, the DC vaccine and CIK cell therapy was associated with mild adverse effects, but was able to induce an immune response and effectively eliminate tumor cells, thereby improving the QOL and prolonging the MST of the patients. IntroductionHepatobiliary and pancreatic cancer (HPC) is a major threat to human health, with an increasing incidence over the last few years. Surgery, chemotherapy and radiotherapy are currently the mainstay of treatment for HPC. Although surgery is the first treatment of choice, early-stage cancer is diagnosed in a limited number of patients (1,2). Furthermore, the hepatobiliary and pancreatic systems exhibit a complex anatomical structure and serve important physiological functions. Consequently, HPC symptoms lack specificity and have typically reached an advanced stage at diagnosis. Radical resection of HPC is not typically performed, and the majority of HPCs are associated with a poor prognosis (3,4). Chemotherapy and radiotherapy are the primary treatments for advanced-stage disease; however, these treatments may result in major health issues and are associated with severe treatment-related toxicity. Furthermore, the overall health status of HPC patients is generally poor, which may prevent them from being eligible for these standard therapies (2,5).In addition to the common factors affecting the prognosis of cancer patients (disease stage, tumor size, lymph node metastasis and radical surgery), individual differences in the immune factors among patients also affect prognosis. As all cancer patients exhibit varying degrees of low immunity and a significant proportion are in an immunosuppressed state, recovering anticancer immunity is a possible approach to cancer treatment. Autologous immune cell therapy has been the fourth most commonly used treatment method for ca...

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“…CIK cells have a major histocompatibility complex (MHC)-independent antitumor ability in both solid and hematologic malignancies. The antitumor activity is primarily related to a high percentage of the CD3 + CD56 + subset (Ma et al, 2012;Nakano et al, 2012). The exact mechanism is still unclear, but primarily relates to the secretion of cytokines to inhibit the growth of tumor cells (Pievani et al, 2011;Wang et al, 2011;Yang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin

Chen

Xiang

Ding

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism. Methods: Tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells. The concentrations of tumor necrosis factor-α (TNF-α) and perforin in the culture medium supernatant were examined by using an enzyme-linked immunosorbent assay (ELISA) kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line. Results: The concentrations of TNF-α and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml (P<0.01) and 3.39 ng/ml (P<0.05). The killing rate of the group TEX-CIK was 33.35%, lower than that of the group N-CIK (47.35% (P<0.01)). The population of CD3

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Cytokine-induced killer (CIK) cell therapy for patients with hepatocellular carcinoma: efficacy and safety

Cited by 75 publications

References 24 publications

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine-induced killer cell therapy in hepatobiliary and pancreatic cancer

Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin

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