Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives (original) (raw)
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Dendritic Cell Vaccine for Recurrent High-Grade Gliomas in Pediatric and Adult Subjects
Neurosurgery, 2013
BACKGROUND: Although there have been significant advances in understanding the basic pathogenesis of glioblastoma multiforme, the median survival of patients has changed little in the past 25 years. Recent studies have suggested that immune modulation through dendritic cell (DC) vaccines may stimulate the immune system against tumor antigens and potentially increase survival. OBJECTIVE: To determine whether the use of adjuvant vaccination with autologous DCs (matured in situ after being loaded with tumor cell lysate derived from autologous refractory gliomas) is safe, feasible, and beneficial for adult and pediatric patients with recurrent high-grade gliomas. METHODS: The study design is a single-center, nonrandomized, open phase I clinical trial. A total of 20 patients with malignant gliomas will be enrolled preoperatively over 2 years. Patients will be given adjuvant vaccination with autologous DCs loaded with tumor lysate after maximal safe surgical resection. EXPECTED OUTCOMES: Using topical imiquimod before vaccination, it is anticipated that the immune response in vaccinated patients and potentially Overall survival will be greater than that demonstrated in the literature. We anticipate that there will be minimal side effects (minor dermatitis) associated with this treatment. DISCUSSION: In the current trial, we assess immune response, safety, and survival using a novel vaccine protocol developed in Belgium that seems to markedly increase survival of certain subjects. Nevertheless, larger randomized clinical studies need to be performed to evaluate fully the efficacy of this therapy for both recurrent and newly diagnosed glioblastoma.
DENDRITIC CELL VACCINATION IN PATIENTS WITH MALIGNANT GLIOMAS
Neurosurgery, 2006
OBJECTIVE: Despite recent advances in neurosurgical resection techniques, radiation therapy, and chemotherapy, malignant gliomas continue to have a dismal prognosis because relapses are unavoidable. METHODS: Dendritic cell vaccination has recently emerged as a promising type of active immunotherapy that aims to induce rather than transfer specific antitumor immune responses in patients. Active immunotherapy is the only type of immunotherapy able to induce immunological memory. RESULTS: Although an increasing number of small clinical trials show safety, feasibility, and immunological and clinical responses, this technology requires further clarification of some critical basic and clinical issues before its presumed place in the treatment of malignant gliomas can be specified. This article addresses the basic and clinical pitfalls that, more than with conventional therapies, may interfere with the potential benefits of this approach. CONCLUSION: Considering the particular mechanisms involved in the immune modulation of tumor biology using dendritic cell-based vaccinations, the authors summarize the arguments in favor of a further, appropriate assessment of this technology.
Adjuvant dendritic cell-based tumour vaccination for children with malignant brain tumours
Pediatric Blood & Cancer, 2009
13.5 months (range: 1.4-85.6). All patients with MB/PNET died (median OS 5.7 months; range 4.3-51.2). One patient with ependymoma is still alive at 22.3 months FU. The other three patients died at, respectively, 7.7, 30.1 and 31.5 months. Two patients with ATRT are still alive at, respectively, 34.1 and 52.6 months FU. The third patient died at 50.5 months. No severe adverse events were noticed. Conclusions. In this exploratory study, HGG and ATRT seem to respond more favourably to vaccination than MB/PNET and ependymoma. Although preliminary, our results are promising and support further testing of DC-based immunotherapy in new treatment protocols for HGG and ATRT.
Dendritic cell vaccination for glioblastoma multiforme: Clinical experience and future directions
Proceedings of the 2014 6th International Advanced Research Workshop on In Silico Oncology and Cancer Investigation - The CHIC Project Workshop (IARWISOCI), 2014
Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain cancer. Since median overall survival with multimodal standard therapy is only 15 months, there is a clear need for additional effective and long-lasting treatments. Dendritic cell (DC) vaccination is an experimental immunotherapy being tested in several Phase I and Phase II clinical trials. In these trials, safety and feasibility have been proven, and promising clinical results have been reported. On the other hand, it is becoming clear that not every GBM patient will benefit from this highly personalized treatment. Defining the subgroup of patients likely to respond to DC vaccination will position this option correctly amongst other new GBM treatment modalities, and pave the way to incorporation in standard therapy. This review provides an overview of GBM treatment options and focuses on the currently known prognostic and predictive factors for response to DC vaccination. In this way, it will provide the clinician with the theoretical background to refer patients who might benefit from this treatment.
Journal of translational medicine, 2018
Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax-L) to standard therapy for newly diagnosed glioblastoma. After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) ha...
ImmunoTargets and Therapy, 2014
Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain cancer. Since median overall survival with multimodal standard therapy is only 15 months, there is a clear need for additional effective and long-lasting treatments. Dendritic cell (DC) vaccination is an experimental immunotherapy being tested in several Phase I and Phase II clinical trials. In these trials, safety and feasibility have been proven, and promising clinical results have been reported. On the other hand, it is becoming clear that not every GBM patient will benefit from this highly personalized treatment. Defining the subgroup of patients likely to respond to DC vaccination will position this option correctly amongst other new GBM treatment modalities, and pave the way to incorporation in standard therapy. This review provides an overview of GBM treatment options and focuses on the currently known prognostic and predictive factors for response to DC vaccination. In this way, it will provide the clinician with the theoretical background to refer patients who might benefit from this treatment.
Journal of neurosurgery, 2004
Treatment of malignant glioma is difficult and discouraging. Even after resection and maximal adjuvant therapy, the prognosis remains poor. The authors sought a novel form of treatment, such as stimulating the patient's own immune response against the tumor, and developed a protocol of tumor vaccination in which autologous dendritic cells (DCs) were used in patients with recurrent malignant glioma. A 4-year-old girl was treated by means of biopsy sampling and radiotherapy for a rolandic low-grade glioma. Ten years later, a Grade III recurrence was discovered and treated with subtotal resection, interstitial radiation, six courses of oral temozolomide, and 12 courses of oral VP 16. At the end of the chemotherapy cycle, a new rapidly growing recurrence was diagnosed. A macroscopically complete resection was performed. Afterward, the girl was vaccinated with autologous DCs that had been pulsed ex vivo with the homogenate of the resection specimen. She received six vaccines in total...
Current Oncology
Background: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients’ long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. Methods: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “glioblastoma multiforme”, “dendritic cell”, “vaccination”, “immunotherapy”, “immune system”, “immune response”, “chemotherapy”, “recurrence”, and “temozolomide”. Among the 157 screened, only 15 articles were eligible for the final analysis. Results: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822–2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882–2.248, p = 0.754). In contrast, DCV led to significantly longer 1-yea...