Immunotherapy. 2012 Oct;4(10):1031-42. doi: 10.2217/imt.12.107.
Dendritic cell-based vaccination for renal cell carcinoma: challenges in clinical trials.
1Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
After decades of research, dendritic cell (DC)-based vaccines for renal cell carcinoma have progressed from preclinical rodent models and safety assessments to Phase I/II clinical trials. DC vaccines represent a promising therapy that has produced measurable immunological responses and prolonged survival rates. However, there is still much room to improve in terms of therapeutic efficacy. The key issues that affect the efficiency and reliability of DC therapy include the selection of patients who will respond best to treatment, the proper preparation and administration of DC vaccines, and a combination of DC vaccination with other immune-enhancing therapies (e.g., removal of Tregs, CTLA-4 blockade and lymphodepletion). Additional antiangiogenic agents will hopefully lead to greater survival benefits for patients in early disease stages. This review focuses on the different approaches of DC-based vaccination against renal cell carcinoma and potential strategies to enhance the efficacy of DCvaccination.
Keywords: cytokine-induced killer cell; dendritic cell; immune monitoring; renal cell carcinoma; tumor vaccine
Cancer Immunol Immunother. 2012 Sep;61(9):1407-13. doi: 10.1007/s00262-012-1207-7. Epub 2012 Jan 26.
Quality of life during dendritic cell vaccination against metastatic renal cell carcinoma.
1Cell Therapy Unit, Department of Urology, Innsbruck Medical University and K1 Center Oncotyrol, A Center for Personalized Cancer Medicine, Innrain 66a, 6020 Innsbruck, Austria.
Patients with metastatic renal cell carcinoma (RCC) undergoing cytokine or targeted therapies may show a remarkable decline in quality of life (QoL). We wanted to evaluate QoL in patients with metastatic RCC undergoing therapeutic vaccination with dendritic cells (DCs). In a cross-sectional analysis, QoL was therefore assessed in RCC patients participating in three consecutive clinical trials of DC vaccination. Before the first and after the third vaccination with DCs, patients completed a QoL questionnaire (EORTC QLQ-C30, version 3). Data were transformed into scale scores and analysed using SPSS 12.0 software. Mean values of the resulting scores obtained before and after DC vaccination were compared using students t test and Wilcoxon rank-sum test. P < 0.05 was considered statistically significant. The questionnaire was completed by 55 of 71 patients (compliance rate, 77.5%) who had a median age of 58.7 years (from 30 to 75 years). No significant reductions in functioning scales including physical, emotional and social criteria as well as symptom scores, which assess typical symptoms of tumour therapies, were observed indicating that QoL remained high during DC vaccination. Significant correlations were found between overall survival and functional as well as symptom scores. Our data indicate that DC vaccination, which is a personalised treatment modality, maintains QoL and thus represents an attractive nontoxic treatment option for patients with metastatic RCC. It will be important to identify the most effective conditions of DC vaccinationincluding combinations with other therapeutics to maximise clinical efficacy while still preserving QoL.
Keywords: Active immunotherapy; Dendritic cells; Cancer vaccine; Renal cell carcinoma; Quality of life
Anticancer Res. 2015 Mar;35(3):1575-82.
Matched-pair analysis of dendritic cell versus targeted-therapy in patients with metastatic renal cell carcinoma.
1Departments of Internal Medicine III, University of Bonn, Bonn, Germany.
2Department of Urology, University of Bonn, Bonn, Germany.
3Center for Integrated Oncology, University of Bonn, Bonn,
Although targeted-therapy (TT) for patients with metastatic renal cell cancer (mRCC) has shown an improved outcome, their prognosis is still very poor. Immunotherapy with dendritic cells (DC) as one promising new treatment tries to fight cancer by boosting the patient’s own immune system. The present analysis matches two different methods of treatment against mRCC, namely sequential TT versus DC vaccine therapy, by comparison of long-term overall survival (OS).
PATIENTS AND METHODS:
Data of patients treated with DC vaccines (N=30) in three clinical phase I/II trials (1999-2003) and patients treated with clinical standard targeted-therapy (N=30) at the University Hospital of Bonn (2010-2013) were analyzed regarding their OS, as well as specific characteristics such as number and localization of metastatic sites.
The mean OS from the first treatment was significantly higher in the TT than in the DC group (48 versus 21 months, range=3-85 months versus 1-57 months, respectively; p=0.0002). Patients with one (p=0.036) or two metastases (p=0.037) and especially patients with bone metastases (52 versus 12 months; p<0.0001) benefited significantly from TT. However, there was no significant difference between therapy types in patients with lung (p=0.147) or liver (p=0.745) metastases, or in patients with more than two metastatic sites (p=0.074).
Targeted therapy is an effective treatment against mRCC, but is limited due to common adverse events and a higher toxicity when combinations of different-targeted agents are used. Immunotherapy with DC vaccines seems to be a potent and well-tolerated therapy against mRCC, possibly showing higher benefit for patients with specific sites of metastasis, and should be investigated as a co-treatment with TT in further studies.
Dendritic cells; immunotherapy; metastases; renal cell carcinoma; sequential therapy; targeted-therapy