A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma

Dong, Hui; Li, Qiang; Wang, Jian; Zhang, Ti; Da-Lu, Kong

doi:10.1016/j.dld.2008.04.007

Cited by 144 publications

(128 citation statements)

References 21 publications

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“…24 CIK treatment has not been shown to improve OS of patients with HCC after curative resection in several other studies. 24,25 Our results suggested that CIK therapy reduced recurrence and death in the earlier post-operative period, but its efficacy failed to achieve any benefit in longterm survival. Recently, Lee et al reported a multicenter trial using CIK as an adjuvant therapy for early stage HCC after curative treatments (which included surgical resection, radiofrequency ablation, and percutaneous ethanol injection).…”

Section: Discussionmentioning

confidence: 81%

“…In another RCT for HCC after curative resection, no significant difference was found in the DFS of HCC between patients who received three courses of CIK and those who received six courses. 25 On the other hand, Pan et al reported patients who received more than eight cycles of CIK transfusion exhibited significantly better survival than those patients who received <8 cycles. 27 In a recent RCT, patients who received 16 cycles of CIK infusion in 60 weeks after curative treatments had significantly better OS and RFS.…”

Section: Discussionmentioning

confidence: 99%

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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: 81%

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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“…The use of immunosuppressive drugs, such as CsA and FK506, prevented the degranulation of CIK cells that is induced by CD3-TCR stimulation; however, the drugs were unable to block the cytotoxicity that was triggered by the interaction with tumor targets. In addition, the degranulation induced by target cells was unaffected by CsA and FK506 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)21). Therefore, the use of immunosuppressive drugs may not affect the efficacy of CIK.…”

Section: Discussionmentioning

confidence: 91%

“…Liver allograft rejection is mediated by a primary response of T lymphocytes, followed by the infiltration of the graft and mixed inflammatory reactions. The proliferation of mononuclear leukocytes inside the allograft is a prominent feature of acute and chronic rejection (13). Therefore, a large number of infused activated T cells may pose a potential risk to the allograft.…”

Section: Introductionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report

Fang

Liu

et al. 2016

Oncology Letters

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Abstract. Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the most lethal cancers worldwide. Immunotherapy based on the direct attack of tumor cells and the stimulation of an antitumor immune response may represent a novel strategy to control HCC recurrence and metastasis. The present study reports the case of a patient with HCC, and describes the safety and feasibility of successful administration with a mass of autologous activated T cells on numerous occasions subsequent to liver transplantation (LT), in order to kill the residual tumor cells and stimulate the immune system. A large number of infused activated T cells may pose a potential risk to the allograft. However, no acute or delayed adverse effects of cytokine-induced killer cell (CIK) therapy, or other symptoms of secondary acute host-versus-graft disease (HVGD), were observed. These observations demonstrate the relatively low toxicity of CIK infusion to a patient that has undergone LT, and more importantly, they demonstrate the feasibility of this immunotherapy for the patient, following successful LT.

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“…CIK cell therapy represents a realistic novel option in the field of cancer therapy as it consistently demonstrates strong anti-tumor activity and improves the overall survival time of cancer patients when used alone, or when combined with other conventional therapies. Since 1991, CIK cell therapy has been evaluated as an adoptive immunotherapy for cancer patients in a number of clinical trials, including in patients with HCC (28,(30)(31)(32)(33). For example, Pan et al (34) reported that CIK cell treatment as an adjuvant therapy for postoperative hepatocellular carcinoma patients could increase overall survival rates compared with surgery alone.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of RetroNectin-activated cytokine-induced killer cell therapy in the treatment of advanced hepatocelluar carcinoma

Wang

Kellner

et al. 2016

Oncology Letters

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Abstract. The present study aimed to investigate the efficacy of RetroNectin-activated cytokine-induced killer cell (R-CIK) therapy in advanced hepatocellular carcinoma patients as compared with conventional chemotherapy, a comparison that has not yet been thoroughly studied. From January 2010 to October 2013, 74 patients with an initial diagnosis of advanced hepatocelluar carcinoma were enrolled in the study. Patients were assigned to one of two treatment arms: patients in arm 1 (n=37) received R-CIK treatment as the first line therapy, whereas those in arm 2 (n=37) received chemotherapy as the first line treatment. The primary end point measured in this study was median overall survival (mOS). Median progression-free survival time (mPFS) and 1-and 2-year survival rates were recorded as secondary end points. Kaplan-Meier analysis was performed on all mOS and mPFS data, and treatment hazard ratios were established using the Cox proportional hazards model. The 1-year survival rate in treatment arm 1 was 42.47% vs. 24.89% in arm 2 (95% CI, 24.91-59.01% vs. 12.10-40.02%, P=0.066); the 2-year survival rates were 21.24 and 5.53% (95% CI, 4.60-45.86 vs. 0.46-21.06%, P= 0.106) in arms 1 and 2, respectively; the mPFS in arm 1 was 4.37 vs. 3.90 (x 2 = 0.182, P=0.670) in arm 2; and the mOS in arm 1 was 14.03 months vs. 9.46 months(x 2 =4.406, P=0.036) in arm 2. Calculations of univariate analyses of arm 1, R-CIK cycles ≥6, KPS >70, AFP ≤400 ng/ml, and findings of no vascular invasion and no extra-hepatic metastasis were potential predictive factors (P<0.05). Calculations from multivariate analyses similarly identified these factors as potentially having predictive value (P<0.05). The main adverse effects of R-CIK therapy included fever and headache pain. R-CIK treatment may prolong mOS in advanced hepatocellular carcinoma patients compared with conventional chemotherapy. Patients who underwent ≥6 cycles of R-CIK, had KPS scores >70, AFP ≤400 ng/ml, displayed no evidence of vascular invasion, and no extra-hepatic metastasis appeared to have longer survival times compared with other cohorts in the present study.

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A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma

Cited by 144 publications

References 21 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

Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report

Efficacy of RetroNectin-activated cytokine-induced killer cell therapy in the treatment of advanced hepatocelluar carcinoma

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