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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells
Published on: January 6, 2014
Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis
Andreas Draube1, Nela Klein-González, Stefanie Mattheus
1Laboratory for Tumor and Transplantation Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Background:
More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis.
Methodology/Principal Findings:
Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated.
Conclusions/Significance:
As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines.
Insights
Dendritic cell (DC) cancer vaccines show a link between immune response and clinical benefit. Higher DC doses and stronger immune responses correlate with better outcomes in prostate and renal cell cancer (RCC) patients.
Area of Science:
- Immunology
- Oncology
- Clinical Trials
Background:
- Over 200 clinical trials have investigated dendritic cells (DCs) as cancer adjuvants.
- A key question remains whether immune response correlates with clinical outcomes.
- Prostate and renal cell cancer (RCC) were selected for this systematic review and meta-analysis.
Purpose of the Study:
- To determine the link between immune response and clinical outcomes in DC-based cancer immunotherapy.
- To analyze data from clinical trials in prostate and RCC.
- To perform a systematic review and meta-analysis of individual patient data.
Main Methods:
- Systematic literature search of clinical trials with at least 6 patients.
- Individual patient data meta-analysis using conditional logistic regression.
- Analysis of 29 trials with 906 patients (17 prostate cancer, 12 RCC).
Main Results:
- Objective response rates were 7.7% in prostate cancer and 12.7% in RCC.
- Clinical benefit rates (objective response + stable disease) were 54% (prostate) and 48% (RCC).
- Cellular immune response significantly influenced clinical benefit in both cancer types (OR 10.6 for prostate, OR 8.4 for RCC). DC dose also significantly influenced clinical benefit.
Conclusions:
- Demonstrated a statistically significant effect of DC-mediated immune response and DC dose on clinical benefit rate (CBR).
- Findings support DC-based vaccines as a viable immunotherapeutic strategy.
- Highlights the importance of vaccine composition, quality control, and DC maturation status for future development.
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