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Background: To analyze the efficacy and safety of dendritic cell - cytokine - induced killer (DC-CIK) immunotherapy combined with chemotherapy for colorectal cancer. Method: A retrospective analysis was conducted in 116 patients from February 2012 to December 2017, who were divided into postoperative adjuvant chemotherapy group alone, combined DC-CIK immunotherapy group, advanced cancer palliative care group, and palliative care + DC-CIK immunotherapy group, to evaluate cellular immune function, disease-free survival(DFS) and overall survival(OS). Results: In the adjuvant therapy and palliative care group, the percentages of CD3+, CD8+ and NK cells after treatment were significantly lower than before, whereas in the other two groups given DC-CIK immunotherapy, the percentages of CD3+, CD8+, NK and NKT cells after treatment were all higher than before, with a significant increase compared with the chemotherapy group ( P < .05). DFS (42.4 ± 5.26 m) in the group receiving postoperative adjuvant chemotherapy + DC-CIK immunotherapy was significantly longer than that (23.5 ± 2.79 m) in the group only given postoperative adjuvant chemotherapy ( P < .05). OS in the group receiving palliative care + DC-CIK immunotherapy was slightly longer than that in the group only given palliative care for advanced cancer (29 m vs 26 m, P > .05). Conclusion: Combination with DC-CIK immunotherapy could effectively improve cellular immune function. Postoperative adjuvant chemotherapy in combination with DC-CIK immunotherapy could significantly prolong DFS, but palliative care in combination with DC-CIK immunotherapy did not significantly prolong OS in patients with advanced cancer.

Lung cancer remains the leading cause of cancer-related death worldwide. The advent of immune checkpoint inhibitors has led to a paradigm shift in the treatment of metastatic non-small cell and small cell lung cancer. However, despite prolonged overall survival, only a minority of the patients derive clinical benefit from these treatments suggesting that the full anti-tumoral potential of the immune system is not being harnessed yet. One way to overcome this problem is to combine immune checkpoint blockade with different strategies aimed at inducing or restoring cellular immunity in a tumor-specific, robust, and durable way. Owing to their unique capacity to initiate and regulate T cell responses, dendritic cells have been extensively explored as tools for immunotherapy in many tumors, including lung cancer. In this review, we provide an update on the nearly twenty years of experience with dendritic cell-based immunotherapy in lung cancer. We summarize the main results from the early phase trials and give an overview of the future perspectives within this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stevens, Ingels, Van Lint, Vandekerckhove and Vermaelen.)

The Aim of This Study: The purpose of this study is to investigate whether the DC cells combined with CIK cells (DC/CIK) and DC activated cytotoxic T cells (DC-ACT) treatment can promote antitumor response and change the immune indicators by targeting the heterogeneous tumor cell populations at a system level., Methods: In this study, 112 patients with cancer were assigned to the DC/CIK treatment and 116 patients received the DC-ACT therapy. We detected the lymphocyte subsets and other immune indicators pre- and post-treatment to evaluate the changes of patient's immunity and compare the differences in immune status between two adoptive cellular immunotherapies., Results: DC/CIK therapy elevated the percentage of CD3+ HLA-DR+ T cells, NK cells and several serological cytokines such as IL-2, IL-6 after cell infusion ( p < .05). DC-ACT therapy could increase the total CD3 + T cells, CD8 + T cells, CD3+ HLA-DR+ cells and IL-12 cytokines after cell infusion ( p < .05). The levels of IL-4/IFN-γ, IL-4/IL-12 and IL-6/IL-12 were reduced significantly in the DC-ACT group compared with DC/CIK group. These observations suggested that DC-ACT therapy has more dominance to induce Th1 cytokine response instead of skewing toward the Th2 cytokine profile based on the immunomodulatory properties., Conclusions: These results indicated that DC, CIK, and DC-ACT cells exert anti-tumor activity through the different pathways. Thus, this work may provide valuable insights into the clinical curative effect evaluation of immunocyte therapy and the design of combined immunotherapeutic strategies for malignant tumors.

Aim: To assess the efficacy of dendritic cells-cytokine induced killer (DC-CIK) and natural killer (NK) cell-based immunotherapy in treating the low- and intermediate-risk acute myeloid leukemia. Patients & methods: DC-CIK or NK cells were infused once every 3 months for 2-4 cycles to 85 patients. Results & conclusion: The 5-year overall survival (OS) and relapse-free survival (RFS) rates were 90.5 and 65.2%, respectively. The OS of the very favorable, the favorable and the intermediate-risk groups was 94.4, 86.3 and 93.3% (p = 0.88), and the RFS 83.3, 81.8 and 62.2% (p = 0.14), respectively. The OS and RFS of the 60 patients treated with DC-CIK alternating with NK cells were better than the 25 patients treated with DC-CIK or NK alone (96.5 vs 71.2%; p = 0.003. 79.5 vs 28.9%; p < 0.001).

Background: Although promising results have recently been reported using dendritic cells (DCs) and cytokine-induced killer cells (CIKs) to treat pancreatic cancer (PC), its clinical effect and safety are associated with some controversy, and lack sufficient evidence. Here, we conducted a meta-analysis of 21 clinical trials to better evaluate the efficacy of DC-CIK immunotherapy in clinical practice to treat PC., Methods: PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data Knowledge Service Platform (WANFANG Data) were searched to identify clinical trials that used DC-CIK immunotherapy for PC. Meta-analysis was performed using RevMan 5.3 and Stata 12.0., Results: A total of 21 clinical trials involving 1549 patients were included. Compared with traditional treatment, DC-CIK immunotherapy improved and increased the clinical indices such as complete remission, partial remission, overall response rate, disease control rate, overall survival (0.5-y OS, 1-y OS, 1.5-y OS, 2-y OS and 3-y OS), interferon γ and CD3+, CD4+, CD4+/CD8+ and CD3+CD56+ lymphocyte. Additionally, DC-CIK immunotherapy reduced stable disease, progression disease, mortality, CD8+, CD4+CD25+CD127 low lymphocyte and interleukin-4. Furthermore, it showed a low incidence of adverse reactions (22%)., Conclusion: In contrast to traditional therapy, DC-CIK immunotherapy not only shows improved short-term effect, long-term effect and immunologic function, but also reduces mortality and negative immunoregulatory index, and shows mild adverse reactions. This is the first study to evaluate the clinical effect and safety of DC-CIK immunotherapy for PC, and it indicated that DC-CIK immunotherapy may be suitable for patients with advanced PC or intolerance to radiotherapy and chemotherapy., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells (DCs) and cytokine-induced killer cells (CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored., Aim: To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs, combined with different conventional treatments of HCC., Methods: We performed a literature search on PubMed and Web of Science up to February 15, 2019. Long-term efficacy (overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis., Results: A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio (RR) = 1.07; 95% confidence interval (CI): 1.01-1.13, P = 0.02], 1 year (RR = 1.12; 95%CI: 1.07-1.17, P < 0.00001), 3 years (RR = 1.23; 95%CI: 1.15-1.31, P < 0.00001) and 5 years (RR = 1.26; 95%CI: 1.15-1.37, P < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo (RR = 0.50; 95%CI: 0.36-0.69, P < 0.0001) and 1 year (RR = 0.82; 95%CI: 0.75-0.89, P < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe, feasible treatment., Conclusion: Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients' prognosis by increasing overall survival and reducing cancer recurrence., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Background: Advanced non-small cell lung cancer (NSCLC) has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with chemotherapy (CT) in this malignancy., Methods: We have developed a new clinical trial design termed as the prospective patient's preference-based study (PPPS). Consecutive patients (n = 135) with advanced NSCLC were treated with DC-CIK administered with CT or mono-therapy (CT or DC-CIK alone)., Results: For all the patients, the median PFS was 5.7 months and the median OS was 17.5 months. The 1-year PFS and OS rates were 29.4% and 58.2%, respectively. The 1-year PFS and OS rates for DC-CIK plus CT were significantly higher than that in the group of patients who received DC-CIK alone and CT alone (P < 0.05). The number of adoptively infused DC-CIK cells was associated with clinical efficacy. After adjusting for competing risk factors, DC-CIK combined with CT and infused number of CIKs remained independent predictors of PFS and OS. Phenotypic analysis of peripheral blood mononuclear cells showed that CD8+CD28+, and CD8+CD28- T cells, changed significantly in all groups (P < 0.01). The CD3+ T cells increased in the chemotherapy plus immunotherapy and the immunotherapy alone group (P < 0.01), while CD3-CD16+CD56 T cells decreased in the chemotherapy plus immunotherapy and the immunotherapy alone group (P < 0.01)., Conclusions: DC-CIK combined with chemotherapy administration resulted in numerically superior PFS and OS compared with monotherapy in advanced NSCLC.

Cancer is a severe lethal disease. Currently, immunotherapy has become an effective alternative therapeutic approach for cancers. Cytokine-induced killer (CIK) cells have a higher proliferation rate, increased efficacy with few side-effects, and non-MHC-restricted killing after co-culturing with dendritic cells (DCs). Therefore, it has been widely studied and applied in the treatment of cancers. In our study, we explored the antitumor effects of CIK cells co-culturing with DCs pulsed with non-cell derived targeting peptides, which could specifically bind to certain tumor cells. Our results indicated that targeting peptide-loaded DCs could enhance the differentiation and cytotoxicity of CIK cells. Moreover, CIK cells, which were treated with specific targeting peptide-loaded DCs, could effectively and specifically kill tumor cells in vitro and in vivo, as long as tumor cells were pre-coated with the specific binding peptides. In conclusion, targeting peptides could guide DC-CIK to effectively and specifically kill tumor cells which were pre-coated with these targeting peptides and non-cell derived targeting peptide-loaded-DC-CIK may work as a novel means for cancer therapy.

Objective: DC-CIK therapy included DC-CIK cells and Ag-DC-CIK cells. To further confirm whether DC-CIK reconstructs the antitumor immunity and improves the tumor responses and reveals its optimal usage and combination with chemotherapy, we systematically reevaluated all the related studies., Materials and Methods: All studies about DC-CIK plus chemotherapy for NSCLC were collected from the published and ongoing database as CBM, CNKI, VIP, Wanfang, ISI, Embase, MEDLINE, CENTRAL, WHO-ICTRP, Chi-CTR, and US clinical trials (established on June 2017). We evaluated their methodological bias risk according to the Cochrane evaluation handbook of RCTs (5.1.0), extracted data following the predesigned data extraction form, and synthesized the data using meta-analysis., Results: We included 28 RCTs (phase IV) with 2242 patients, but most trials had unclear bias risk. The SMD and 95% CI of meta-analysis for CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, CD4 + /CD8 + T cell ratio, CIK cells, NK cells, and Treg cells were as follows: 1.85 (1.39 to 2.31), 0.87 (0.65 to 1.10), 1.04 (0.58 to 1.50), 0.75 (0.27 to 1.22), 3.87 (2.48 to 5.25), 1.51 (0.99 to 2.03), and -2.31(-3.84 to -0.79). The RR and 95% CI of meta-analysis for ORR and DCR were as follows: 1.38 (1.24 to 1.54) and 1.27 (1.20 to 1.34). All differences were statistically significant between DC-CIK plus chemotherapy and chemotherapy alone. Subgroup analysis showed that only DC-CIK cells could increase the CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, and CD4 + /CD8 + T cell ratio. In treatment with one cycle or two cycles and combination with NP or GP, DC-CIK could increase the CD4 + /CD8 + T cell ratio. All results had good stability., Conclusions: DC-CIK therapy can simultaneously improve the antitumor immunity and tumor responses. DC-CIK therapy, especially DC-CIK cells, can improve antitumor immunity through increasing the T lymphocyte subsets, CIK cell, and NK cells in peripheral blood. The one cycle to two cycles may be optimal cycle, and the NP or GP may be optimal combination.

Background: Immunotherapy is emerging as a new treatment strategy for gastric cancer(GC). However, the efficacy and safety of this technique remain unclear. This meta-analysis aimed to assess the effect of cytokine-induced killer cell (CIK)/dendritic cell-cytokine-induced killer cell (DC-CIK) treatment for GC after surgery., Methods: Hazard ratio (HR), overall survival (OS) rates, and disease-free survival (DFS) rates were calculated using a Mantel-Haenszel (M-H) fixed-effects model (FEM), and results were displayed using forest plots. Publication bias was assessed by Begg test, and data were presented using funnel plots. Date robustness was assessed by the trim and fill method. Descriptive analysis was performed on T lymphocytes and adverse effects., Results: In total, 9 trials, including 1216 patients, were eligible for inclusion in this meta-analysis. Compared with the control group, the HR for OS was 0.712 (95% confidence interval [CI] 0.594-0.854) and 0.66 (95% CI 0.546-0.797) for overall (DFS). The risk ratio (RR) of the 3 and 5-year OS rate was 1.29 (95% CI 1.15-1.46) and 1.73 (95% CI 1.36-2.19), respectively. The RR for the 3 and 5-year DFS rate 1.40 (95% CI 1.19-1.65) and 2.10 (95% CI1.53-2.87), respectively. The proportion of patients who were CD3+, CD4+, and CD4+/CD8+ increased in the cellular therapy groups. No fatal adverse reactions were noted., Conclusion: Chemotherapy combined with CIK/DC-CIK therapy after surgery resulted in low HR, and significantly increasing OS rates, DFS rates, and T-lymphocyte responses in patients with GC.

Background Aims: Dendritic cell (DC)-based immunotherapy has recently been reported frequently in the treatment of hepatocellular carcinoma (HCC); however, its efficacy remains controversial. In this study, we aimed to evaluate the clinical efficacy of DC-based immunotherapy on HCC by conducting a systematic review and meta-analysis., Methods: PubMed, Cochrane Library, Embase and Web of Science were searched to identify clinical trials on DC-based immunotherapy for HCC published up to January 31, 2018. The articles were selected according to pre-established inclusion criteria and methodologic quality, and publication bias were evaluated., Results: A total of 1276 cases from 19 clinical trials were included. Compared with traditional treatment, further DC-based therapy enhanced the CD4 + T/CD8 + T ratio (standardized mean difference: 0.68, 95% confidence interval [CI] 0.46-0.89, P < 0.001); increased the 1-year, 18-month and 5-year progression-free survival (PFS) rate and the 1-year, 18-month and 2-year overall survival (OS) rate (relative risk > 1, P < 0.05), prolonged the median PFS time (median survival ratio [MSR]: 1.98, 95% CI: 1.60-2.46, P < 0.001) and median OS time (MSR: 1.72, 95% CI: 1.51-1.96, P < 0.001). Adverse reactions were mild., Conclusions: DC-based therapy not only enhanced anti-tumor immunity, improved the survival rate and prolonged the survival time of HCC patients, but it was also safe. These findings will provide encouraging information for further development of DC-based immunotherapy as an adjuvant treatment for HCC. However, the results must be interpreted with caution because of the small study numbers, publication bias and the various of study designs, pre-treatment and therapeutic processes of DCs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Primary liver cancer is a sort of the most common solid tumors occurred in the digestive system. The incidence and mortality rate maintain at a high level, thus leading to heavy economic and psychological burdens for patients. Next-generation biological therapy, such as cellular immune treatment, improves the medicine efficacy. Cytokine-induced killer (CIK) cells can effectively clear residual tumor lesion and inhibit metastasis or recurrence. Dendritic cells (DCs) can specifically eliminate tumor cells via modulating cellular immune function of the host. This study aimed to investigate the function of DC+CIK combined treatment on rat liver model and its effect on immune functions., Materials and Methods: RH-35 tumor cell was used to prepare live cancer model on Wistar rats, which were further divided into control, CIK and DC+CIK groups, in which rats received autograft CIK and DCs. Tumor size was later measured along with liver function index. The secretions of IFN-γ, IL-4, and TNF-α were measured by Real-time PCR and Western blotting., Results: Both CIK and DC+CIK treatment significantly reduced tumor size and improved liver function, increased secretion of IFN-γ, IL-4, and TNF-α, decreased Bcl-2 expression and enhanced Bax expression (p < 0.05 compared to control group). DC+CIK combined therapy presented significantly better efficacy than CIK did., Conclusions: DC+CIK combined therapy can protect the host against tumors invasion via modulating body immune or liver function, regulating apoptosis/anti-apoptosis balance, which shows better efficacy than CIK alone, and can work as a novel biological therapeutic strategy for liver cancer.

Background: Surgical resection combined with adjuvant chemotherapy is considered as the gold-standard treatment for advanced colorectal cancer patients. These patients have a poor 5-year survival rate of 5% or less. Furthermore, a large dose of chemotherapy can produce adverse side effects and severe toxicity. Therefore, this retrospective study aimed to evaluate the efficacy of dendritic cell-cytokine-induced killer (DC-CIK) cell infusion as an adjuvant therapy in patients with advanced colorectal cancer combined with first-line treatment., Methods: A total of 142 patients with stage III/IV colorectal carcinoma who had been treated with first-line therapy were included in this study. Among these patients, 71 patients received first-line treatment only (non-DC-CIK group), while the other 71 patients who had similar demographic and clinical characteristics received a DC-CIK cell infusion combined with first-line treatment (DC-CIK group). These patients were followed up until August 2014. Data were analyzed by Kaplan-Meier and Cox regression., Results: Our results showed that the 5-year overall survival (OS) rate for the DC-CIK group versus the non-DC-CIK group was 41.3 versus 19.4% (p = 0.001) and the 5-year progression-free survival (PFS) rate for the DC-CIK group versus the non-DC-CIK group was 57.4 versus 33.6% (p = 0.022)., Conclusions: Our results showed that patients with advanced colorectal cancer might benefit from DC-CIK immunotherapy combined with first-line therapy by significantly prolonging 5-year OS and PFS.

Regulatory T cells (Tregs) suppress antitumor immune responses. Cycles of Dendritic cells (DC) vaccination combined with cytokine-induced killer (CIK) cells (DC/CIK) treatment were significantly related with good prognosis. Therefore, we investigated whether increased cycles of immunotherapy could decrease frequency of Tregs in patients with resected non-small cell lung cancer (NSCLC). Previous study from our laboratory has determined that the optimal cutoff point of the cycle count was 3cycles. We examined the levels of Tregs and the related cytokines by flow cytometric and cytokine analysis in these patients after more than (≥) 3cycles or less than (<) 3cycles of DC/CIK cell treatment. Significant reduction of Tregs frequency, Treg-generated cytokines level and recurrence rate were presented in patients received with ≥3cycles of DC/CIK cell treatment compared with patients with <3cycles of treatment. Interestingly, Tregs frequency and the related cytokines level were similar between patients suffered tumor recurrence and patients without recurrence in both groups. Together, our findings reveal that increased cycle count of DC/CIK cell immunotherapy contribute to decline of Tregs frequency and cancer recurrence rate in patients with resected NSCLC., (Copyright © 2017. Published by Elsevier B.V.)

This study aims to compare the efficacy of different treatments for nude mice transplanted with HT-29 colon carcinoma cell line. BalB/C nude mice were transplanted with HT-29 colon carcinoma cell line and randomly divided into four groups, with 5 mice in each group: blank control group, DC-CIK group, Huaier Granule group, and Huaier Granule group combined with DC-CIK group (combined treatment group). For DC-CIK group and combined treatment group, 1×106 DC-CIK cells were injected via the tail vein 4 days after transplantation. The injection was performed twice weekly for a total of 2 weeks. For Huaier Granule group and combined treatment group, Huaier Granule was administered at the dose of 20 g/60 g, by dissolving 20 g of Huaier granules in 600 ml of pure water. Intragastric administration of 0.2 ml of granules was performed once daily for 3 weeks. For the blank control group, equal volume of normal saline was given. Tumor size and body weight of nude mice were measured every 2 days during the 3-week treatment. The mice were sacrificed at the end of treatment to harvest tumors. Key genes of the signaling pathway were detected by RT-PCR. At the end of treatment, mice in combined treatment group, DC-CIK group and Huaier Granule group remained stable emotionally with normal mobility and water and food intake. However, in the blank control group, the mobility was restricted starting from the third week and the mice were on the verge of dying. The expression of PI3KR1, Akt, Wnt1, CTTNB1, Notch1, Notch2 and Notch3 genes were all downregulated significantly in the combined treatment group compared with DC-CIK group and Huaier Granule group (P<0.05). Therefore, the combined treatment of Huaier Granule combined with DC-CIK achieved the best effect in nude mice transplanted with HT-29 colon carcinoma cell line.

Purpose: To systematically evaluate the efficacy and safety of Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells (CIK/DC-CIK) immunotherapy in treating advanced colorectal cancer (CRC) patients., Results: 29 trials including 2,610 CRC patients were evolved. Compared with chemotherapy alone, the combination of chemotherapy with CIK/DC-CIK immunotherapy significantly prolonged the overall survival rate (OS) and disease-free survival rate (DFS) (1-5 year OS, P < 0.01; 1-, 2-, 3- and 5-year DFS, P < 0.01). The combined therapy also improved patients' overall response, disease control rate and life quality (P < 0.05). After immunotherapy, lymphocyte subsets percentages of CD3+, CD3-CD56+, CD3+CD56+ and CD16+CD56+ (P < 0.01) and cytokines levels of IL-2 and IFN-γ (P < 0.05) were increased, while CD4+, CD8+ and CD4+CD25+ and IL-6 and TNF-α did not show significant change (P > 0.05)., Materials and Methods: Clinical trials reporting response or safety of CIK/DC-CIK immunotherapy treating advanced CRC patients and published before September 2016 were searched in Cochrane Library, EMBASE, PubMed, Wanfang and CNKI database. Research quality and heterogeneity were evaluated before analysis. Pooled analyses were performed using random or fixed-effect models., Conclusions: The combination of CIK/DC-CIK immunotherapy and chemotherapy prolong CRC patients' survival time, enhanced patients' immune function and alleviates the adverse effects caused by chemotherapy.

BACKGROUND To determine the effects of dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with malignant pericardial effusion. MATERIAL AND METHODS All patients underwent pericardial puncture and indwelling catheter insertion. After pericardial drainage, the 16 patients in the treatment group received an infusion of 20 mL DCs and CIK cells (>1.0×10¹° cells) and 500,000 U interleukin (IL)-2 for 3 successive days. The 15 control-group patients received 30 mg/m² cisplatin and 500,000 U IL-2 for 3 successive days. The treatment effects were assessed using imaging data. RESULTS The total efficiency and complete remission rates were higher in the treatment group than in the control group at 4 weeks (total efficiency: 87.50% vs. 73.33%; complete remission: 62.50% vs. 46.67%) and 3 months after the treatment (total efficiency: 81.25% vs. 66.67%; complete remission: 50.00% vs. 40.00%; P<0.05 for all). In both groups, the Karnofsky scores for quality of life improved after treatment. However, the curative effects were better in the treatment group than in the control group (P<0.05). The following adverse reactions occurred: fever, 6 treatment-group patients and 3 control-group patients; chest pain, 2 treatment-group patients and 7 control-group patients; gastrointestinal reactions, 1 treatment-group patient and 6 control-group patients; and bone marrow suppression, 1 treatment-group patient and 5 control-group patients. The between-group differences in adverse reactions were significant (P<0.05). CONCLUSIONS The combination of DCs and CIK cells effectively treated malignant pericardial effusion, produced few side effects, and improved the patients' quality of life., Competing Interests: The authors declare that they have no actual or potential conflicts of interest.

Patients with hepatocellular carcinoma (HCC), a fatal cancer, have benefited significantly from TACE (transcatheter arterial chemoembolization) and immunotherapy treatments. Immunotherapy that includes dendritic cells and cytokine-induced killer cells (DC-CIK) in combination with TACE has been extensively applied in cases of HCC. Few decisive conclusions about these combined effects on the outcomes of HCC patients have been reached. Therefore, the present meta-analysis was performed to compare the efficacy of the combined usage of DC-CIK with TACE with a TACE therapy alone on the outcomes of HCC patients. Participants were enrolled in eight eligible trials. The efficiency and safety of TACE followed by DC-CIK immunotherapy (experimental group) and of TACE alone (control group) were compared. The meta-analysis results demonstrated that TACE plus DC-CIK immunotherapy is possibly superior to TACE alone in promoting a better overall response, for half-year, 1-year, and 2-year overall survival (OS), median overall survival (OS) and progression-free survival rates (PFS) in HCC patients. Further studies should be performed to confirm the effect of the combined therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The antitumor activity of cytokine-induced killer (CIK) cells can be increased by co-culturing them with tumor lysate-pulsed dendritic cells (tDCs); this phenomenon has been studied mainly at the population level. Using time-lapse imaging, we examined how CIK cells gather information from tDCs at the single-cell level. tDCs highly expressed CCL5, which bound CCR5 expressed on CIK cells. tDCs strongly induced migration of Ccr5(+/+) CIK cells, but not that of Ccr5(-/-) CIK cells or Ccr5(+/+) CIK cells treated with the CCR5 antagonist Maraviroc. Individual tDCs contacted Ccr5(+/+) CIK cells more frequently and lengthily than with Ccr5(-/-) CIK cells. Consequently, tDCs increased the antitumor activity of Ccr5(+/+) CIK cells in vitro and in vivo, but did not increase that of Ccr5(-/-) CIK cells. Taken together, our data provide insight into the mechanism of CIK cell activation by tDCs at the single-cell level., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The response of hepatocellular carcinoma (HCC) to immunotherapy is often disappointing and new strategies are clearly needed. The aim of the present study was to investigate whether cytokine-induced killer (CIK) cells combined with a dendritic cell vaccination enhanced cytotoxicity against hepatocarcinoma tumor cells in an in vivo animal model., Methods: CIKs and DCs were prepared from C3H/HeJ mice by conventional methods, the dendritic cell (DC) pulsed with a MH134 cell lysate, DC or CIK alone were used as controls. Cell phenotypes were analyzed by flow cytometry, cytokine secretion levels were determined by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was assessed by means of an in vitro lactate dehydrogenase (LDH) release assay. A mouse hepatocarcinoma cell MH134-bearing mice model was established to test the in vivo anti-tumor efficacy of the system., Results: CIK cells combined with DC therapy resulted in significant inhibition of tumor growth compared with the control group, whereas the decrease in tumor growth in mice that had been treated with CIK or DC alone did not reach the level of statistical significance. The combination therapy led to a further increase in the population of cytotoxic T cells (CTLs) in vivo, compared to the CIK or DC alone therapy. In addition, the combination therapy significantly enhanced cytotoxic activity against MH134 cells., Conclusion: Taken together, these results show that a DC + CIK vaccination is more effective than DC or CIK alone therapy for the treatment of hepatocarcinoma cancer.

Objective: This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy., Methods: 217 patients participated in the follow-up study. CD4+CD25+ proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of CD4+CD25+ proportion more than 5% and less than or equal to 5% in peripheral T cells., Results: Peripheral CD4+CD25+ T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral CD4+CD25+ proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95%CI 1.04, 2.62). Above 5% CD4+CD25+proportion of T cells produced the HR to be 1.76 (95%CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95%CI 1.05, 12.29) in triple negative breast cancer patients., Conclusions: Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral CD4+CD25+T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.

The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P < 0.05). The MRD rate was >0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.

To investigate the clinical efficacy of adoptive immunotherapy using dendritic cells (DC) and cytokine-induced killer (CIK) cells combined with chemotherapy in multiple myeloma. The immunomodulatory effect of the therapy was discussed by detecting the levels of peripheral blood T cell subsets and CD4(+)CD25(+) regulatory cells (Treg). Fifty MM patients were randomly divided into two groups: 24 cases in the simple chemotherapy group and 26 cases in the combined therapy group (chemotherapy plus DC/CIK immunotherapy). The therapeutic efficacy and the proportions of peripheral blood T cell subsets and Treg cells were compared between the two groups. The cellular immunity indicators were also compared, including IL-2, IFN-γ, IL-4, IL-10, AgNORs ratio and TGF-β. After 3 weeks of treatment, the life quality and clinical efficacy of the combined therapy group were superior to those of the simple chemotherapy group (P<0.05). CD3(+)CD8(+) ratio, CD4(+)CD25(+) ratio, CD4(+)CD25(+)/CD4(+) ratio, CD4(+)CD25(+)FoxP3(+)/CD4(+)CD25(+) ratio, IL-4, IL-10 and TGF-β levels of the combined therapy group were obviously lower than those of the simple chemotherapy group (P<0.05). The CD3(+)CD4(+)/CD3(+)CD8(+) ratio, AgNOR ratio, IL-2 and IFN-γ level and positive rate of NKG2D in the combined therapy group were significantly higher than those of the simple chemotherapy group (P<0.05). These results indicated better immunomodulatory effect of the combined therapy. DC/CIK immunotherapy combined with chemotherapy has a good clinical efficacy and prospect for MM, reversing the Th1 to Th2 shift and increasing the anti-tumor capacity of the immune system.

Dendritic cells (DCs) have displayed the promising potential in cancer immunity. How to enhance DCs immunotherapeutic effect in cancer targeted immunotherapy and prevention is still a great challenge. Herein, we report for the first time the allogenic DCs and tumor cell fused vaccine combined with cytokine induced killing cells (CIKs) for targeted imaging and enhanced immunotherapeutic efficacy of gastric cancer (GC). The fused vaccine was prepared by PEG mediated fusion between mature DCs and inactive gastric cancer MGC803 cells. The immunotherapeutic and prophylactic potential of the fused cells (FCs) were evaluated in tumor-bearing, post-surgery and tumor free mice models. The migration and homing process of near infrared region quantum dots (NIR-QDs) labeled FCs were investigated by real-time animal imaging system. Results showed that the FCs and FC + CIKs could trigger the tumor-specific CTLs against GC cells, target the tumor tissue initiatively and enhance the prophylactic effects, suppress the tumor growth remarkably in vivo. The potential mechanism is also investigated. In conclusion, allogenic DCs and tumor cell fused vaccine can be used for targeted imaging and enhanced immunotherapeutic efficacy of GC, and the FC + CIKs strategy own great potential in clinical applications such as early therapy and prevention of tumor-metastasis and relapse in near future., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study aimed to analyze the clinical effects of dendritic cell (DC) and cytokine-induced killer (CIK) immunotherapy combined with chemotherapy on patients with metastatic breast cancer. Twenty patients were included into this study who were diagnosed as metastatic breast cancer (MBC). DC and CIK were augmented by in vitro culture and then rein fused into body through vein.The pain relief rate (RR), toxic and side effects of chemotherapy, immunity functions and living quality of patients were observed. DC and CIK cells were induced by the autologous peripheral blood mononuclear cells (PBMC). Meanwhile, flow cytometry was used to measure T cell subsets and natural killer T (NKT) cells in patients in the two groups before and after the biological treatment. After DC and CIK were rein fused into the patients body, no severe side-effect was found. It was also found that cellular immunotherapy combined with chemotherapy the immunotherapy of cells improved the immunity, the living quality of patients and the disease control rate (DCR). In conclusion, cellular immunotherapy produces small side effects; it combined with chemotherapyis able to improve the DCR and living quality of patients and prolong their lives.

Dendritic cell (DC) vaccination and cytokine-induced killer (CIK) cell therapy (DC/CIK) have shown limited success in the treatment of advanced non-small cell lung cancer (NSCLC). To investigate the reason for this limited success, the effects of DC/CIK cell therapy on the immune responses of tumor-bearing patients and patients with resected NSCLC were evaluated. In the total 50 patients studied, the serum concentrations of the Th2 cytokines (IL-4 and IL-10) in tumor-bearing patients were significantly higher than those with resected NSCLC before immunotherapy. The post-therapy Th1 cytokine (IFN-γ) level in patients with resected NSCLC significantly increased from the pre-therapy level. In contrast, significantly enhanced post-therapy Th2 cytokine (IL-4 and IL-10) levels were found in tumor-bearing patients. The intracellular staining assay revealed that DC/CIK cell therapy increased the IFN-γ-producing T lymphocyte (CD8(+)IFN-γ(+)) frequency in patients with resected NSCLC, but these lymphocytes were not found in tumor-bearing patients. Furthermore, overproduction of vascular endothelial growth factor (VEGF) in tumor-bearing patients showed a statistically positive correlation with IL-4, suggesting that VEGF might be responsible for the predominance of serum Th2 cytokines. In a word, tumor-bearing patients developed a Th2-dominant status that could not be reversed toward Th1 following immunotherapy. A combined regiment of DC vaccination and CIK cell therapy with other treatments to overcome systemic Th2-dominant immune response might improve the current clinical benefit., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients., Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits., Results: An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05)., Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Background: To evaluate the therapeutic efficacy of dendritic cells (DC) alone, cytokine-induced killer (CIK) cells alone and the combination of DC and CIK cells in the treatment of breast cancer, we performed a systemic review of the relevant published clinical studies, collectively referred to as DC-CIK cell therapy., Methods: Six hundred thirty-three patients with breast cancer were assigned to cohorts, and a meta-analysis was conducted., Results: The treatment of breast cancer with DC-CIK cells was associated with a significantly improved 1-year survival (P = 0.0001). The Karnofsky performance status scale of the patients treated with DC-CIK cells was significantly improved compared with that of the non-DC-CIK group (P < 0.0001). The percentage of T cells (CD3(+), CD4(+) and CD4(+)CD8(+)), CD16(+) monocytes, and CD3(+)CD56(+) natural killer T cells in the peripheral blood of cancer patients was significantly increased (P ≤ 0.05), whereas the percentage of CD4(+)CD25(+) regulatory T cells was not significantly decreased (P = 0.32) in the DC-CIK treatment group compared with the non-DC-CIK group. The levels of interleukin-2, interleukin-12, tumor necrosis factor-α, interferon-γ, and nucleolar organizer region protein in the peripheral blood of cancer patients, which reflect immune function, were significantly increased (P < 0.001) after DC-CIK cell treatment. Furthermore, after DC-CIK treatment, the average levels of the alpha-fetoprotein, cancer antigen embryonic antigen and carbohydrate antigen tumor markers were decreased (P < 0.00001)., Conclusions: DC-CIK cell therapy markedly prolongs survival time, enhances immune function, and improves the efficacy of the treatment of breast cancer patients., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the safety and effectiveness of erlotinib plus DC/CIK in maintenance therapy of advanced non-small cell lung cancer. After 4 cycles of the 2-drug regimen treatment with platinum, the 54 patients with non-small cell lung cancer in phase IIIb or IV reached stable or beyond stable stages. The patients were then randomly divided into 2 groups. One group was treated with erlotinib therapy (erlotinib group), and the other was treated with DC/CIK plus erlotinib (DC/CIK plus erlotinib group). The progression-free survival of the erlotinib group and the DC/CIK plus erlotinib group was 3.98 months (95% CI, 3.56-4.40) and 5.02 months (95% CI, 4.32-5.72) (P=0.002), respectively. The median overall survival of the erlotinib group and the DC/CIK plus erlotinib group was 9.9 months (95% CI, 9.1-10.6) and 10.5 months (95% CI, 9.6-11.4) (P=0.29), respectively. The levels of CD3, CD4, and CD8 were significantly different before and after the treatment in the DC/CIK plus erlotinib group, but not in the erlotinib group. There was no significant difference in toxicity between the 2 groups. In conclusion, there was no statistically significant difference in overall survival between DC/CIK plus erlotinib and erlotinib as maintenance therapy. DC/CIK plus erlotinib was well tolerated with a manageable safety profile.

Dendritic cells (DC) play a crucial role in the induction of an effective antitumor immune response. Cytokine-induced killer (CIK) cells, a subset of T lymphocytes, have the capacity to eliminate cancer cells. This study was to evaluate the correlation between the frequency of DC/CIK immunotherapies following regular chemotherapy, the time-to-progression (TTP), and overall survival (OS) of advanced non-small lung cancer patients. Sixty patients with IIIB-IV non-small-cell lung carcinoma (NSCLC) were enrolled from August 2007 to December 2009 and were randomized into two groups. All 60 patients received four courses of navelbine-platinum (NP) chemotherapy. In one group, 30 patients were treated with adoptive autologous DC/CIK cell transfusion twice every 30 days. In the other group, the patients received immunotherapies more than twice every 30 days. The adverse effects, TTP, and OS were evaluated between the two groups. Median survival time of all 60 patients was 13.80 months. The 1-, 2-, and 3-year overall survival rates were 60.0, 21.7, and 15.0 %, respectively. The 1-, 2-, and 3-year overall survival rates of patients receiving more than two immunotherapies were 63.3, 30.0, and 23.3 %, and the rates of those receiving two immunotherapies were 56.7, 13.3, and 6.7 %, respectively. The difference between the two groups was statistically significant (P = 0.037). Compared with patients in the fewer immunotherapies group, TTP in the group receiving more immunotherapies significantly prolonged, with the median improving from 6.2 months (95 % CI, 5.35-9.24) to 7.3 months (95 % CI, 5.45-6.95; P = 0.034). The adverse effects of chemoimmunotherapy were tolerable. Advanced NSCLC patients can benefit from the combination of DC/CIK immunotherapies following conventional chemotherapy. More than two immunotherapies improved TTP and OS of those patients in this study.

Aim: To investigate whether autologous dendritic cell (DC)-cytokine-induced killer (CIK) cell therapy is able to improve the therapeutic efficacy of chemotherapy in colon cancer., Methods: We conducted a systematic review of published papers from the sources of MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors using predefined database templates. The quality of the data from individual papers was also assessed. The effects of chemotherapy were compared with those of chemotherapy in combination with DC-CIK immunotherapy. The pooled analysis was performed using the data from random or fixed-effect models., Results: Seven trials matched our inclusion criteria (n = 533). The overall analysis showed significant survival benefit [one-year overall survival (OS), P < 0.0001; two-year OS, P = 0.009; three-year OS, P = 0.002] in favor of DC-CIK immunotherapy combined with chemotherapy. Disease-free survival (DFS) rate was improved after the combination of DC-CIK immunotherapy and chemotherapy (one-year DFS, P < 0.0001; two-year DFS, P = 0.002; three-year DFS, P = 0.02). An improved overall response rate (P = 0.009) was also observed in patients who received DC-CIK therapy. Furthermore, the analysis of T-lymphocyte subsets in peripheral blood indicated that the number of CD4⁺ T cells significantly increased in the DC-CIK plus chemotherapy group (P < 0.05)., Conclusion: The combination of DC-CIK immunotherapy and chemotherapy was superior in prolonging the survival time and enhancing immunological responses.

Purpose: This retrospective study determined the delayed-type hypersensitivity (DTH) skin test and safety of dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC) patients., Methods: DTH and safety of the immunotherapy were recorded. The overall survival (OS) and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates., Results: Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST) (198.00 days) was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days) (P = 0.02). For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy (P = 0.41). MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone (P = 0.41)., Conclusions: DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS.

Background: We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients., Patients and Methods: Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS)., Results: Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports., Conclusion: Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

We aim to study the therapeutic effects of HBsAg-activated DCs and cytokine-induced killer (CIK) cells as adoptive immunotherapy in patients with Chronic Hepatitis B (CHB). Autologous HBsAg-activated DC-CIK cells were infused into patients with CHB to evaluate their effect on HBV-DNA, HBsAg, ALT, etc. The viral load in the treatment group decreased significantly (P < 0.001), while that in the control group did not decrease (P > 0.05). Twenty-one patients (63.6% efficiency) in the treatment group had a viral response (≥2 log decrease in viral load), while four patients (14.8% efficiency) from the control group had a viral response. There were significant differences in the viral responses of the two groups (the control group 63.6% versus the control group 14.8%, P < 0.001). We concluded that the immunity was enhanced after HBsAg activation in DCs and CIK cells. Reinfusion of autologous HBsAg-activated DC-CIK cells inhibited HBV proliferation in 21 of 33 (63.6%) patients., (© 2013 John Wiley & Sons Ltd.)

Cytokine-induced killer (CIK) cells show cytolytic activity against tumor. The purpose of this study was to evaluate the antitumor effect of dendritic cell (DC)-activated CIK cells in vitro and their clinical efficacy of DC-activated CIK cells in combination with chemotherapy (abbreviated below as chemotherapy plus DC + CIK) in patients with advanced non-small-cell lung cancer (NSCLC). A paired study was performed between 61 patients treated with chemotherapy alone (group 1) and 61 patients treated with chemotherapy plus DC + CIK cells (group 2). In group 2, 36 patients with adenocarcinoma and 18 patients with squamous cell carcinoma were analyzed for the survival rate. Compared to unstimulated CIK cells, DC-activated CIK cells significantly enhanced antitumor activity, increased the ratio of CD3(+)CD56(+) cells, promoted cell proliferation and lessened cell apoptosis. In the paired study, the 1- and 2-year overall survival rates in group 2 were 57.2 and 27.0 %, which were significantly higher than that of group 1 (37.3 and 10.1 %) (P < 0.05). There was no significant difference in the survival rate between the adenocarcinoma and squamous carcinoma patients in group 2. The present study suggests that DC-activated CIK cell has enhanced antitumor effects and chemotherapy plus DC + CIK cells improved the clinical outcomes of chemotherapy for advanced NSCLC patients.

Objectives: To investigate the possibility of culturing dendritic cells (DCs) and cytokine-induced killer (CIK) cells, obtained at initial diagnosis of AML in elderly patients, and to investigate the safety and efficacy of treatment with autologous DCs and CIK cells when administered to these patients in combination with low-dose chemo therapy., Methods: DCs and CIK cells obtained at initial diagnosis of AML in elderly patients were cultured and used in combination with low-dose chemo therapy to treat these patients (immunotherapy group). Elderly patients with AML treated only with low-dose chemotherapy served as the control. Before treatment and on day 7 after treatment with autologous DCs and CIK cells, T cell subsets and cytokine levels were evaluated in the immunotherapy group., Results: A total of 21 elderly patients with AML were included in the immunotherapy group and 23 in the control group. The clinical efficacy in the immunotherapy group was greater than in the control group. The percentages of T cell subsets and cytokine levels after immunotherapy treatment were significantly higher than before the treatment., Conclusion: Immuno therapy with autologous DCs and CIK cells was found to be a promising candidate for treatment of AML in elderly patients.

Background: Lung cancer is the leading cause for cancer-related mortality and morbidity, and the survival of late-stage non-small cell lung cancer (NSCLC) remains poor. We hereby evaluate conventional chemotherapy followed by immunotherapy using dendritic cells and cytokine-induced killer cells in the treatment for late stage of NSCLC., Methods: Twenty-eight untreated patients suffered from IIIB to IV NSCLC were enrolled in the study between August 2004 and October 2005, and all received four courses of vinorelbine-platinum (NP) chemotherapy. Fourteen of them received conventional NP chemotherapy followed by vaccinated with CEA (605-613) peptide-pulsed autologous dendritic cells and CIK cells. Vaccination was repeated at 30-day intervals for 4 cycles. The adverse effects, time to progression (TTP), and overall survival (OS) in each group were evaluated., Results: The adverse effect as a result of chemoimmunotherapy was mild and tolerable. Rash, acne, and pruritus were more frequent in the chemoimmunotherapy group than in the chemotherapy group (64.2% vs. 7.1%, P = 0.004). Non-infectious fever was more frequent in the chemoimmunotherapy group than in the chemotherapy group (71.4% vs. 21.4% P = 0.02). Less grade 3/4 fatigue was observed in patients receiving chemoimmunotherapy: 7.1% versus 57.1% in chemotherapy group, P = 0.01. Compared with patients in chemotherapy group, time to progression in chemoimmunotherapy significantly prolonged, with the median improved from 5.2 months (95% CI: 3.3-6.0) to 6.9 months (95% CI: 5.0-8.8) (P = 0.03). The 1-, 2-, and 5-year survival rates were 64.3, 49, and 21.0%, respectively in chemoimmunotherapy group. Overall survival rate showed no statistically difference between two groups (P = 0.18)., Conclusions: Chemoimmunotherapy could alleviate adverse effects of conventional chemotherapy and prolong survival for patients with late-stage NSCLC.

Objective: To evaluate the effect and safety of Chinese herbal medicine Lingdankang Composite (LDK) combined dendritic cell-cytokine induced killer cells (DC-CIK) in treating leukemia., Methods: Subjects were selected from leukemia patients who achieved hematological complete remission (HCR) but not achieved molecular biological remission (MBR), or with minimal residual leukemia (MRL) positive. Twenty patients, 19 of acute leukemia and 1 of chronic myelocytic leukemia, were enrolled. DC and CIK from patient's peripheral blood monocyte were separated respectively by blood cell separator, then DC-CIK was obtained through respective culture followed with mixed cultivation of them, and was infused back to the patient self via intravenous injection. The back infusion of DC-CIK was performed once every 15-20 days for 4-6 times in total. Meantime, LDK was administered orally every day., Results: In the 20 patients treated, 4 case of HCR achieved MBR, the negatively reversed marker gene was AML1/ETO in 1 case, CBFbeta/MYH11 in 1, bcr/abl in 1, and the other 1 was IgH gene rearrangement; 3 patients with positive MRL were reversed to negative. The 3-year CR rate was 75% with a medium CR period of 25 months (10-37 months). Except transient fever and chill in 5 cases, no other remarkable adverse reaction happened during or after DC-CIK infusion., Conclusion: The combined treatment of LDK and autologous DC-CIK in treating patients with HCR shows an obvious effect of clearing MRL, it is the appropriate choice for curing leukemia of HCR, and is safety for intravenous infusion, so it has potential clinical prospect.

Background: Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are functionally impaired in patients with chronic hepatitis B (CHB). Adoptive immunotherapy can suppress hepatitis B virus (HBV) replication in CHB patients, but whether it can restore the functionality of mDCs and pDCs remains unknown., Methods: Autologous cytokine-induced killer (CIK) cells obtained from 14 CHB patients were transfused back to patients, case by case, to observe the effect of CIK-cell treatment on the frequency and functionality of mDCs and pDCs in CHB patients during a 24-week follow-up investigation., Results: Seven virological responders exhibited a sustained decrease in HBV load after CIK-cell transfusion; another seven non-virological responders showed only sustained high levels of HBV load during the 24-week period following CIK-cell transfusion. The rate of hepatitis B e antigen loss or seroconversion was also higher in virological responders than in non-virological responders. Importantly, we found that the frequency and cytokine-producing capacity of mDCs and pDCs increased significantly in virological responders, but not in non-virological responders. In addition, these patients exhibited a close correlation between restoration DC subsets and a decrease in HBV DNA load, rather than a change in the alanine aminotransferase level., Conclusion: Cytokine-induced killer-cell treatment reduced HBV DNA load in some CHB patients; the efficiency at least partially correlates with the restoration of frequency and functionality of mDCs and pDCs.