Cytokine‐induced killer (CIK) cells represent an exceptional T‐cell population uniting a T cell and natural killer cell‐like phenotype in their terminally differentiated CD3+CD56+ subset, which ...features non‐MHC‐restricted tumor‐killing activity. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures. We established the international registry on CIK cells (IRCC) to collect and evaluate clinical trials for the treatment of cancer patients in 2010. Moreover, our registry set new standards on the reporting of results from clinical trials using CIK cells. In the present update, a total of 106 clinical trials including 10,225 patients were enrolled in IRCC, of which 4,889 patients in over 30 distinct tumor entities were treated with CIK cells alone or in combination with conventional or novel therapies. Significantly improved median progression‐free survival and overall survival were shown in 27 trials, and 9 trials reported a significantly increased 5‐year survival rate. Mild adverse effects and graft‐versus‐host diseases were also observed in the studies. Recently, more efforts have been put into the improvement of antitumoral efficacy by CIK cells including the administration of immune checkpoint inhibitors and modification with chimeric antigen receptorc. The minimal toxicity and multiple improvements on their tumor‐killing activity both make CIK cells a favorable therapeutic tool in the clinical practice of cancer immunotherapy.
Cytokine‐induced killer (CIK) cells featuring non‐MHC‐restricted tumor‐killing activity have provided encouraging results in clinical studies. Here, we update the clinical data including a total of 106 trials enrolled in the international registry on CIK cells (IRCC) established in 2010. The recent multiple improvements both on antitumoral efficacy and toxicity make CIK cells an important therapeutic approach in clinical practice of cancer immunotherapy.
Emerging evidence from the numerous clinical trials involving cytokine-induced killer (CIK) cell therapy suggests that its optimization in combination with other contemporary cancer therapies in a ...complementary manner (rather than as competition) will be a key to combat cancer.
Purpose
Cytokine-induced killer (CIK) cells represent an exceptional T cell population uniting a T cell and natural killer cell like phenotype in their terminally differentiated CD3
+
CD56
+
subset, ...which features non-MHC-restricted tumor-killing activity. CIK cells are expandable from peripheral blood mononuclear cells and mature following the addition of certain cytokines. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures.
Methods
Therefore, we established the international registry on CIK cells in order to collect and evaluate data about clinical trials using CIK cells for the treatment of cancer patients. Moreover, our registry is expected to set new standards on the reporting of results from clinical trials using CIK cells. Clinical responses, overall survival (OS), adverse reactions and immunologic effects were analyzed in 45 studies present in our database. These studies investigated 22 different tumor entities altogether enrolling 2,729 patients.
Results
A mean response rate of 39 % and significantly increased OS, accompanied by an improved quality of life, were reported. Interestingly, side effects of CIK cell treatment were minor. Mild fevers, chills, headache and fatigue were, however, seen regularly after CIK cell infusion. Moreover, CIK cells revealed numerous immunologic effects such as changes in T cell subsets, tumor markers, cytokine secretion and HBV viral load.
Conclusion
Due to their easy availability and potent antitumor activity, CIK cells emerged as a promising immunotherapy approach in oncology and may gain major importance on the prognosis of cancer.
Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may ...benefit patients with this disease.
In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group.
Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval CI, 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patients who received interferon alone. Overall survival in the combination-therapy group did not differ significantly from that in the interferon group (hazard ratio, 0.96; 95% CI, 0.76 to 1.20; P=0.70). Median overall survival times in the interferon group, the temsirolimus group, and the combination-therapy group were 7.3, 10.9, and 8.4 months, respectively. Rash, peripheral edema, hyperglycemia, and hyperlipidemia were more common in the temsirolimus group, whereas asthenia was more common in the interferon group. There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group (P=0.02).
As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival. (ClinicalTrials.gov number, NCT00065468 ClinicalTrials.gov.).
Undeniably, immunotherapy has markedly improved the survival rate of cancer patients. The scenario is no different in lung cancer, where multiple treatment options are now available and the inclusion ...of immunotherapy yields better clinical benefits than previously used chemotherapeutic strategies. Of interest, cytokine-induced killer (CIK) cell immunotherapy has also taken a central role in clinical trials for the treatment of lung cancer. Herein, we describe the relative success of CIK cell therapy (alone and combined with dendritic cells as DC/CIKs) in lung cancer clinical trials and discuss its combination with known immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Additionally, we provide insights into the findings of several preclinical in vitro/in vivo studies linked to lung cancer. In our opinion, CIK cell therapy, which recently completed 30 years and has been approved in many countries, including Germany, offers tremendous potential for lung cancer. Foremost, when it is optimized on a patient-by-patient basis with special attention to the patient-specific genomic signature.
Background
In some breast and gynaecologic cancer centres in Germany, patients participate in their own case discussion in multidisciplinary tumour conferences (MTCs), where treatment recommendations ...are discussed and finalized. However, the extent to which patients in MTCs are involved in decision‐making on treatment recommendations remains largely unexplored. Hence, this study investigates how recommendations are communicated to patients and the extent to which the interactions with patients in MTCs are in line with shared decision‐making (SDM).
Methods
In this observational study, we audio‐recorded MTCs with patient participation in three breast and gynaecologic cancer centres in Germany. We qualitatively analysed the data with regard to content and linguistic aspects.
Results
We analysed 82 case discussions. Recommendations made during MTCs were regarding (i) treatment options, (ii) treatment initiation, (iii) next (treatment) steps and (iv) whether a treatment method should be initiated at all. The decision about recommendations depended in part on patients' preferences or further course/further outcomes. Although the purpose of MTCs is to provide recommendations, some recommendations were framed as the final decision. The majority of the decision‐making conversation could be characterized as option talk (78%), during which patients were mostly proposed only one (treatment) option.
Conclusions
This study establishes limited SDM in MTCs with patient participation. By indicating choices and thereby creating awareness of choices among patients, MTCs with patient participation could be used to foster SDM implementation.
Patient or Public Contribution
Two representatives of a large self‐help organization for patients with breast cancer assisted the research project, particularly, in discussing the results.
Histone deacetylase (HDAC) inhibitors have enormous therapeutic potential as effective epigenetic regulators, and now with the focus on the selective HDAC6 inhibitor in ongoing clinical trials, more ...advantages over other non-selective pan-HDAC inhibitors are foreseeable. As it is of paramount importance to understand the complex regulatory web of mutual interactions involving epigenetic machinery and non-coding genome in regulating gene expression, herein, we investigated the intriguing interactions between HDAC6-induced lncRNA (LINC00152) and its possible sponge miRNA (hsa-miR-499a-5p) in multiple myeloma.
Glioblastoma multiforme (GBM) is probably the only tumor in which a unique epigenetic alteration, namely methylation of the MGMT gene, possesses direct clinical relevance. Now with the emergence of ...aberrant N6 methyladenosine (m6A) modifications (the most common epigenetic modification of mRNA, closely linked to the autophagy process) in cancer, the epi-transcriptomic landscape of GBM pathobiology has been expanded. Considering this, herein, we systematically analyzed m6A regulators, assessed their correlation with autophagy-related genes (ATG), and established a long non-coding RNAs (lncRNA)-dependent prognostic signature (m6A-autophagy-lncRNAs) for GBM. Our analysis identified a novel signature of five long non-coding RNAs (lncRNAs: ITGA6-AS1, AC124248.1, NFYC-AS1, AC025171.1, and AC005229.3) associated with survival of GBM patients, and four among them clearly showed cancer-associated potential. We further validated and confirmed the altered expression of two lncRNAs (AC124248.1, AC005229.3) in GBM associated clinical samples using RT-PCR. Concerning the prognostic ability, the obtained signature determined high-/low-risk groups in GBM patients and showed sensitivity to anticancer drugs. Collectively, the m6A-autophagy-lncRNAs signature presented in the study is clinically relevant and is the first attempt to systematically predict the potential interaction between the three key determinants (m6A, autophagy, lncRNA) in cancer, particularly in GBM.
This analysis aims at evaluating the impact of multidisciplinary tumor boards on clinical outcome of multiple tumor entities, the effect of the specific number of multidisciplinary tumor boards and ...potential differences between the tumor entities.
By a matched-pair analysis we compared the response to treatment, overall survival, relapse or disease free survival and progression free survival of patients whose cases were discussed in a tumor board meeting with patients whose cases were not. It was performed with patients registered in the cancer registry of the University of Bonn and diagnosed between 2010 and 2016. After the matching process with a pool of 7262 patients a total of 454 patients with 66 different tumor types were included in this study.
First, patients with three or more multidisciplinary tumor board meetings in their history show a significantly better overall survival than patients with no tumor board meeting. Second, response to treatment, relapse free survival and time to progression were not found to be significantly different. Third, there was no significant difference for a specific tumor entity.
This study revealed a positive impact of a higher number of multidisciplinary tumor boards on the clinical outcome. Also, our analysis hints towards a positive effect of multidisciplinary tumor boards on overall survival.
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