Anlotinib and anti-PD-1 mAbs perfected CIK cell therapy for lung adenocarcinoma in preclinical trials.

Murine cytokine-induced killer (CIK) cells are heterologous cells that kill various allogeneic and isogenic tumors and have functional and phenotypic characteristics of natural killer cells and T lymphocytes. However, the effect of CIK cells alone on solid tumor therapy is only limited. To enhance the therapeutic effect, it is vital to discover a mix of several therapy approaches. Immune cell function is inhibited by abnormal tumor vessels and the tumor microenvironment, which block lymphocyte entry into tumor tissue. To increase the effectiveness of CIK cells' antitumor activity, antivascular therapy and CIK cell therapy can be combined. Furthermore, anlotinib is a tiny drug with multitarget tyrosine kinase inhibitors that can block cell migration, delay angiogenesis, and decrease blood vessel density. Compared with other antiangiogenesis drugs, anlotinib stands out due to the wider target of action and lower effective dose. In this work, anlotinib and murine CIK cells were coupled to boost CD3+ T cell infiltration, CD3+CD4+ T cell infiltration, and expression of granzyme B and interferon γ from CD3+CD8+ T cells, which increased the antitumor activity. Through the generation of cytotoxic cytokines by T lymphocytes, the therapeutic group using anti-PD-1 monoclonal antibodies in conjunction with anlotinib and CIK cells was more successful than the group receiving dual therapy. The preclinical study contributes to exploring the therapeutic alternatives for patients with lung adenocarcinoma, thus prolonging their lives.

Cytokine-Induced Killer Cell Immunotherapy Combined With Gemcitabine Reduces Systemic Metastasis in Pancreatic Cancer: An Analysis Using Preclinical Adjuvant Therapy-Mimicking Pancreatic Cancer Xenograft Model.

OBJECTIVES: To evaluate the efficacy and safety of cytokine-induced killer (CIK) cell therapy in pancreatic cancer. METHODS: An orthotopic murine model of pancreatic cancer and adjuvant therapy-mimicking xenograft murine model that underwent splenectomy was created. Eighty mice were randomized into four groups: the control, gemcitabine alone, CIK alone, and CIK with gemcitabine groups. The tumor growth was monitored using bioluminescence imaging once weekly. RESULTS: In the orthotopic murine model, the treatment groups showed a significantly longer survival than the control group (median: not reached vs 125.0 days; 95% confidence interval, 119.87-130.13; P = 0.04); however, the overall survival did not differ significantly among the treatment groups (P = 0.779). The metastatic recurrence rate and overall survival were also not significantly different among the groups in the adjuvant therapy-mimicking xenograft murine model (P = 0.497). However, the CIK and gemcitabine combination suppressed the metastatic recurrence effectively, with recurrence-free survival being significantly longer in the CIK with gemcitabine group than in the control group (median, 54 days; 95% confidence interval, 25.00-102.00; P = 0.013). CONCLUSIONS: The combination of CIK and gemcitabine suppressed systemic metastatic recurrence, with promising efficacy and good tolerability in an adjuvant setting of pancreatic cancer.

Novel Immune Cell-Based Therapies to Eradicate High-Risk Acute Myeloid Leukemia.

Adverse genetic risk acute myeloid leukemia (AML) includes a wide range of clinical-pathological entities with extremely poor outcomes; thus, novel therapeutic approaches are needed. Promising results achieved by engineered chimeric antigen receptor (CAR) T cells in other blood neoplasms have paved the way for the development of immune cell-based therapies for adverse genetic risk AML. Among these, adoptive cell immunotherapies with single/multiple CAR-T cells, CAR-natural killer (NK) cells, cytokine-induced killer cells (CIK), and NK cells are subjects of ongoing clinical trials. On the other hand, allogeneic hematopoietic stem cell transplantation (allo-HSCT) still represents the only curative option for adverse genetic risk AML patients. Unfortunately, high relapse rates (above 50%) and associated dismal outcomes (reported survival ~10-20%) even question the role of current allo-HSCT protocols and emphasize the urgency of adopting novel effective transplant strategies. We have recently demonstrated that haploidentical allo-HSCT combined with regulatory and conventional T cells adoptive immunotherapy (Treg-Tcon haplo-HSCT) is able to overcome disease-intrinsic chemoresistance, prevent leukemia-relapse, and improve survival of adverse genetic risk AML patients. In this Perspective, we briefly review the recent advancements with immune cell-based strategies against adverse genetic risk AML and discuss how such approaches could favorably impact on patients' outcomes.

Combination of thermal ablation and activated functional killer cells immunotherapy for cancer: A retrospective study.

PURPOSE: The purpose was to evaluate the effect of thermal ablation combined with activated functional killer (AFK) cells immunotherapy for patients with malignant tumors. MATERIALS AND METHODS: A cohort of 10 patients with malignancies received thermal ablation combined with AFK cells immunotherapy. Progression-free survival (PFS), overall survival, laboratory test, and postoperative complications were assessed. RESULTS: The success rate of the combination therapy was 100% and no severe complications occurred. Five patients maintained in PFS (50%) during the follow-up. The median PFS was 11 months (range 3.5-16.75 months). The hemoglobin (P = 0.023), hematocrit (P = 0.034), and lymphocyte ratio (P = 0.023); neutrophil-to-lymphocyte ratio (P = 0.038), neutrophil ratio (P = 0.016), albumin (P = 0.006), and alkaline phosphatase (P = 0.029); CA-125 (P = 0.033); and D-dimer (P = 0.011) changed significant after ablation. Whereas the white blood cell count (P = 0.003), neutrophil count (P = 0.024), lymphocyte count (P =0.003), monocyte ratio (P = 0.008), and eosinophil ratio (P = 0.005) changed significantly after combination therapy. The lymphocytes (P = 0.001) in the surviving patients increased more significantly after treatment. After the combination therapy, the percentage of CD3 + cells (P = 0.016) and CD3+ CD8+ cells (P = 0.002) increased, while CD3-CD16+ CD56+ (P = 0.002) and CD4+/CD8+ (P = 0.016) decreased. CONCLUSION: Combination of thermal ablation and AFK cells immunotherapy is a safe and effective method for patients with malignancy. And adoptive immunotherapy with AFK cells may be helpful to prevent recurrence after thermal ablation in patients with advanced cancer.

High Complete Response Rate in Patients With Metastatic Renal Cell Carcinoma Receiving Autologous Cytokine-Induced Killer Cell Therapy Plus Anti-Programmed Death-1 Agent: A Single-Center Study.

Background and Objective: The results of the CheckMate 025 trial established the status of nivolumab in the second-line treatment of metastatic renal cell carcinoma (mRCC), with an objective response rate (ORR) of 25% and a complete response (CR) rate of 1%. Thus, the efficacy of anti-programmed death (PD)-1 antibodies in the second-line treatment of mRCC requires improvement. The purpose of this study was to explore the clinical efficacy and safety of anti-PD-1 agents combined with cytokine-induced killer (CIK) cell therapy for refractory mRCC. Patients and Methods: Patients with mRCC refractory to previous targeted therapy were included in this study. All patients received anti-PD-1 plus CIK cell therapy. The ORR and CR rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. Results: CR was observed in seven of the 29 patients, and partial response was observed in five patients. The ORR was 41.4% and the median PFS was 15.0 months. Up to the last follow-up, 15 patients died with an average survival time of 37 months. Among the patients who achieved a CR, one experienced cerebellar metastasis 18.8 months after discontinuation, but achieved CR again after localized gamma knife and 1-month axitinib treatment. This regimen was tolerated well and there was no treatment-related death. Conclusions: Combination therapy with anti-PD-1 and CIK cell therapy is safe and effective in patients with mRCC refractory to previous targeted therapy. The high CR rate and long disease-free survival even after long-term discontinued therapy suggest that this combination treatment may represent a potential curative regimen for this type of malignancy.

Analysis of the Clinical Efficacy of Dendritic Cell -cytokine Induced Killer Cell-based Adoptive Immunotherapy for Colorectal Cancer.

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.

Multidirectional Strategies for Targeted Delivery of Oncolytic Viruses by Tumor Infiltrating Immune Cells.

Oncolytic virus (OV) immunotherapy has demonstrated to be a promising approach in cancer treatment due to tumor-specific oncolysis. However, their clinical use so far has been largely limited due to the lack of suitable delivery strategies with high efficacy. Direct 'intratumoral' injection is the way to cross the hurdles of systemic toxicity, while providing local effects. Progress in this field has enabled the development of alternative way using 'systemic' oncolytic virotherapy for producing better results. One major potential roadblock to systemic OV delivery is the low virus persistence in the face of hostile immune system. The delivery challenge is even greater when attempting to target the oncolytic viruses into the entire tumor mass, where not all tumor cells are equally exposed to exactly the same microenvironment. The microenvironment of many tumors is known to be massively infiltrated with various types of leucocytes in both primary and metastatic sites. Interestingly, this intratumoral immune cell heterogeneity exhibits a degree of organized distribution inside the tumor bed as evidenced, for example, by the hypoxic tumor microenviroment where predominantly recruits tumor-associated macrophages. Although in vivo OV delivery seems complicated and challenging, recent results are encouraging for decreasing the limitations of systemically administered oncolytic viruses and an improved efficiency of oncolytic viral therapy in targeting cancerous tissues in vitro. Here, we review the latest developments of carrier cell-based oncolytic virus delivery using tumor-infiltrating immune cells with a focus on the main features of each cellular vehicle.

Cytokine-induced Killer T Cells Enhance the Cytotoxicity Against Carboplatin-resistant Ovarian Cancer Cells.

BACKGROUND/AIM: Ovarian cancer (OC) is typically diagnosed at an advanced stage with limitations for cure. Cytokine-induced killer (CIK) T cell therapy exerts significant cytotoxic effects against cancer cells and reduces the adverse effects of chemotherapy. Herein, we performed a flow cytometry-based method to evaluate the cytotoxicity of peripheral blood mononuclear cells-derived CIK cells against OC cells. MATERIALS AND METHODS: The CIK cells were induced and expanded using an interferon-γ/IL-2-based xeno-free medium system. The cytotoxicity of CIK cells or carboplatin against OC cells was examined. RESULTS: The CIK cells showed an NK-like phenotypic characteristic and dose-dependently increased cytotoxicity against OC cells. We found that the number of advanced OC cells, which were more resistant to carboplatin, was dramatically decreased by an additional one-shot CIK treatment. CONCLUSION: CIK cells have a potent cytotoxic ability that would be explored as an alternative strategy for cancer treatment in the near future.

CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma.

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.

5 years of clinical DC-CIK/NK cells immunotherapy for acute myeloid leukemia - a summary.

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).

Cell transfer-based immunotherapies in cancer: A review.

In cell transfer therapy (CTT), immune cells such as innate immune-derived natural killer cells and dendritic cells as well as acquired immune-related T lymphocytes such as tumor-infiltrating lymphocytes and cytokine-activated or genetically modified peripheral blood T cells are used in the management of cancer. These therapies are increasingly becoming the most used treatment modality in cancer after tumor resection, chemotherapy, and radiotherapy. In adoptive cell transfer, the lymphocytes isolated from either a donor or the patient are modified ex vivo and reinfused to target malignant cells. Transferring in vitro-manipulated immune cells produces a continuous antitumor immune response. In this review, we evaluate the recent advances in CTT for the management of various malignancies.

Dendritic Cells Therapy with Cytokine-Induced Killer Cells and Activated Cytotoxic T Cells Attenuated Th2 Bias Immune Response.

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.

Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and therapeutic efficacy of adjuvant cytokine-induced killer (CIK) cells to minimally invasive therapies in unresectable hepatocellular carcinoma (u-HCC). MATERIALS AND METHODS: Hundred patients diagnosed with having u-HCC in our department from January 1, 2001, to July 31, 2018, were recruited. Forty-three patients received microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) together with autologous CIK cell treatment (TACE + MWA + CIK group), whereas 57 patients received TACE and MWA only (TACE + MWA group). Postprocedural complications and cumulative therapeutic effects were assessed in all patients. The disease control rate, median survival time (MST), and cumulative survival rate were compared between the cohorts using the Kaplan-Meier method and unpaired Student's t-tests. RESULTS: The overall response (complete response [CR] + partial response [PR]) rate was 74.42% (32/43) and 77.19% (44/57) for TACE + MWA + CIK and TACE + MWA groups, respectively (P = 0.243). Those of the TACE + MWA + CIK group had better rates of disease control (CR + PR + stable disease) in contrast to the TACE + MWA group (87.72% vs. 79.07%, respectively) but this failed to achieve statistical significance (P = 0.748). Based on the Kaplan-Meier survival graphs, those of the TACE + MWA + CIK groups possessed markedly increased overall survival (41 months vs. 24 months, P = 0.002) and progression-free survival (17 months vs. 10 months, P = 0.023) rates in compared to the TACE + MWA group. Survival rates were raised also TACE + MWA + CIK group than in TACE + MWA group (P = 0.002), with a MST of 6.13 ± 0.83 months and 11.61 ± 1.59 months in the TACE + MWA + CIK and TACE + MWA groups, respectively. Patients in the TACE + MWA + CIK group were not reported to have any severe complications. CONCLUSION: CIK cell immunotherapy as an adjuvant to TACE and MWA enhanced long-term prognosis and improved quality of life in patients with u-HCC. This regimen may be recommended as a novel treatment regime in u-HCC patients.

Dendritic Cell-Based Immunotherapy in Lung 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.

Clinical effect and safety of dendritic cell-cytokine-induced killer cell immunotherapy for pancreatic cancer: a systematic review and meta-analysis.

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.

PD-L1 expression is a predictive biomarker for CIK cell-based immunotherapy in postoperative patients with breast cancer.

BACKGROUND: A sequential combination of radiochemotherapy/endocrinotherapy and cytokine-induced killer cell (CIK) infusion has been shown to be an effective therapy for post-mastectomy breast cancer based on statistical analysis of the patient population. However, whether an individual could obtain an improved prognosis from CIK cell-based treatment remains unknown. In the present study, we focused on immune microenvironment regulation and specifically investigated the relationship between PD-L1 expression and survival benefit from CIK immunotherapy in breast cancer. METHODS: A total of 310 postoperative breast cancer patients who received comprehensive treatment were enrolled in this retrospective study, including 160 patients in the control group (received chemotherapy/radiotherapy/endocrinotherapy) and 150 patients in the CIK cell treatment group (received chemotherapy/radiotherapy/ endocrinotherapy and subsequent CIK infusion). RESULTS: We found that overall survival (OS) and recurrence-free survival (RFS) were significantly better in the CIK group than that in the control group. PD-L1 expression in tumor tissue sections was showed to be an independent prognostic factor for patients in the CIK treatment group using multivariate survival analysis. Further survival analysis in the CIK group showed that patients with PD-L1 tumor expression exhibited longer OS and RFS. In addition, among all patients who were enrolled in this study, only the patients with PD-L1 expression experienced survival benefits from CIK treatment. CONCLUSIONS: Our study showed the relationship between PD-L1 expression and CIK therapy and revealed that PD-L1 expression in the tumor is as an indicator of adjuvant CIK therapy for postoperative breast cancer.

Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: A meta-analysis.

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.

Pseudoprogression: an indicator for cure in combined immunotherapy?

Pseudoprogression is a unique, uncommon phenomenon that often hints at good prognosis. To date, there has been no report of complete remission after pseudoprogression. Here, we report successful treatment of metastatic renal clear cell cancer, using anti-PD-1 antibodies combined with autologous RetroNectin-activated cytokine-induced killer cells, in two patients who were failed to multitargeted kinase inhibitors. After early pseudoprogression, complete remission was achieved. At present, one patient has stopped therapy for about 1.5 years and is still disease free.

Adjuvant cytokine-induced killer cell immunotherapy for hepatocellular carcinoma: a propensity score-matched analysis of real-world data.

BACKGROUND: Several randomized controlled trials have shown that adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells prolongs recurrence-free survival (RFS) after curative treatment for hepatocellular carcinoma (HCC). We investigated the efficacy of adjuvant immunotherapy with activated CIK cells in real-world clinical practice. METHODS: A total of 59 patients who had undergone curative surgical resection or radiofrequency ablation for stage I or II HCC, and subsequently received adjuvant CIK cell immunotherapy at two large-volume centers in Korea were retrospectively included. Propensity score matching with a 1:1 ratio was conducted to avoid possible bias, and 59 pairs of matched control subjects were also generated. The primary endpoint was RFS and the secondary endpoints were overall survival and safety. RESULTS: The median follow-up duration was 28.0 months (interquartile range, 22.9-42.3 months). In a univariable analysis, the immunotherapy group showed significantly longer RFS than the control group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.80; log-rank P = 0.006). The median RFS in the control group was 29.8 months, and the immunotherapy group did not reach a median RFS. A multivariable Cox proportional hazard analysis showed that immunotherapy was an independent predictor for HCC recurrence (adjusted HR, 0.38; 95% CI, 0.20-0.73; P = 0.004). The overall incidence of adverse events in the immunotherapy group was 16/59 (27.1%) and no patient experienced a grade 3 or 4 adverse event. CONCLUSIONS: The adjuvant immunotherapy with autologous CIK cells after curative treatment safely prolonged the RFS of HCC patients in a real-world setting.