Lancet Oncol. 2014 Jun;15(7):e257-67. doi: 10.1016/S1470-2045(13)70585-0.
Clinical use of dendritic cells for cancer therapy.
1Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium. Electronic address: firstname.lastname@example.org.
2Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research, University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
3Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
4Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
Since the mid-1990s, dendritic cells have been used in clinical trials as cellular mediators for therapeutic vaccination of patients with cancer. Dendritic cell-based immunotherapy is safe and can induce antitumour immunity, even in patients with advanced disease. However, clinical responses have been disappointing, with classic objective tumour response rates rarely exceeding 15%. Paradoxically, findings from emerging research indicate that dendritic cell-based vaccination might improve survival, advocating implementation of alternative endpoints to assess the true clinical potency of dendritic cell-based vaccination. We review the clinical effectiveness of dendritic cell-based vaccine therapy in melanoma, prostate cancer, malignant glioma, and renal cell carcinoma, and summarise the most important lessons from almost two decades of clinical studies of dendritic cell-based immunotherapy in these malignant disorders. We also address how the specialty is evolving, and which new therapeutic concepts are being translated into clinical trials to leverage the clinical effectiveness of dendritic cell-based cancer immunotherapy. Specifically, we discuss two main trends: the implementation of the next-generation dendritic cell vaccines that have improved immunogenicity, and the emerging paradigm of combination of dendritic cell vaccination with other cancer therapies.
PLoS One. 2011 Apr 20;6(4):e18801. doi: 10.1371/journal.pone.0018801.
Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis.
1Laboratory for Tumor and Transplantation Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
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.
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.
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.
Cancer Immunol Immunother. 2007 Apr;56(4):429-45. Epub 2006 Oct 10.
Vaccination therapy in prostate cancer.
1Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milan, Italy.
Radical prostatectomy and radiation therapy provide excellent localized prostate cancer (PC) control. Although the majority of prostate carcinomais nowadays diagnosed at early stages with favourable risk features, in patients up to 30-40% it recurs within 10 years. Furthermore, the lack of effective therapies, once prostate carcinoma becomes refractory to androgen deprivation, mandates the development of alternative therapeutic options. There is a growing interest in harnessing the potency and specificity of anti-tumour immunity through the generation of fully competentdendritic cells and tumour reactive effector lymphocytes. Several strategies to treat or prevent the development of metastatic PC have been explored in clinical trials and are summarized in this review, considering also the feasibility and safety of these approaches. In some cases clinical responses were achieved showing that vaccine-primed T cells induced anti-tumour activity in vivo. The present findings and perspectives of the immunologic interventions in PC patients will be discussed.
Keywords: Prostate cancer; Antigens; Cancer vaccine; Tumour immunity; Androgen deprivation therapy; Radiotherapy