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Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
Published on: August 1, 2013
Adjuvant dendritic cell-based tumour vaccination for children with malignant brain tumours
Hilko Ardon1, Steven De Vleeschouwer, Frank Van Calenbergh
1Department of Neurosurgery, University Hospital Gasthuisberg, Leuven, Belgium. hilko.ardon@uz.kuleuven.be
Insights
Dendritic cell (DC) vaccination shows promise for children with relapsed malignant brain tumors, particularly high grade glioma (HGG) and atypical teratoid-rhabdoid tumors (ATRT). Further research is supported by these preliminary findings.
Area of Science:
- Pediatric Oncology
- Immunotherapy
- Neuro-oncology
Background:
- Dendritic cell (DC)-based vaccination has established use in adult brain tumors.
- This study focuses on the outcomes of DC vaccination in pediatric patients with relapsed malignant brain tumors.
Purpose of the Study:
- To evaluate the efficacy and safety of autologous, monocyte-derived dendritic cell (DC) vaccination in children with relapsed malignant brain tumors.
- To identify tumor types that may respond more favorably to DC-based immunotherapy.
Main Methods:
- Forty-five children with various relapsed malignant brain tumors received DC vaccination loaded with tumor lysate.
- Tumor types included high grade glioma (HGG), medulloblastoma (MB)/primitive neuro-ectodermal tumor (PNET), ependymoma, and atypical teratoid-rhabdoid tumor (ATRT).
- Peripheral blood mononuclear cells (PBMC) were sourced from leukapheresis or fresh blood samples.
Main Results:
- Median overall survival (OS) was 13.5 months for all patients.
- High grade glioma (HGG) patients showed a median follow-up of 35.7 months for survivors.
- Patients with medulloblastoma (MB)/primitive neuro-ectodermal tumor (PNET) had a median OS of 5.7 months, with all patients deceased.
- Atypical teratoid-rhabdoid tumor (ATRT) patients demonstrated promising survival, with two alive at over 34 months.
- No severe adverse events were reported during the vaccination trials.
Conclusions:
- Dendritic cell (DC) vaccination appears more effective in pediatric high grade glioma (HGG) and atypical teratoid-rhabdoid tumors (ATRT) compared to medulloblastoma (MB)/primitive neuro-ectodermal tumors (PNET) and ependymoma.
- Preliminary results suggest DC-based immunotherapy is a promising avenue for HGG and ATRT treatment protocols.
- Further investigation into DC-based immunotherapy for specific pediatric brain tumor types is warranted.
Background:
A large experience with dendritic cell (DC)-based vaccination for malignant brain tumours has been gained in adults. Here we focus on the results obtained in children with relapsed malignant brain tumours.
Procedure:
In total 45 children were vaccinated: 33 high grade glioma (HGG), 5 medulloblastoma (MB)/primitive neuro-ectodermal tumour (PNET), 4 ependymoma and 3 atypical teratoid-rhabdoid tumour (ATRT). Autologous, monocyte-derived DC were generated and loaded with tumour lysate, which was used as source of tumour-associated antigens.
Results:
In 38 patients peripheral blood mononuclear cells (PBMC) were obtained from leukapheresis and in 7 patients from fresh blood samples. 7 HGG patients are still alive with median follow-up (FU) of 35.7 months (range: 12.1-85.6). Median overall survival (OS) was 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.
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