Immune-Oncology: Dendritic Cell Therapy for Glioblastoma
Malignant gliomas are the most prevalent type of primary brain tumors in adults. The most aggressive form, glioblastoma multiforme (GBM, WHO grade IV glioma), is categorized as incurable with average survivals of less than 15 months. The current first-line treatment comprises radical operation and radiotherapy combined with temozolomide chemotherapy (Stupp-protocol), leading to a median survival of 14,6 months. Negative promoter methylation of the MGMT gene confers resistance to Temodal. The median survival for patients with a tumor without promoter methylation of the MGMT gene is 12,7 months compared to 21,7 months for patients with a tumor with promoter methylation of the MGMT gene. Nevertheless, based on the fact that no other successful standard therapy can be provided to the patients, Temodal is still the standard treatment for all GBM IV patients. Salvage treatments upon recurrence are palliative at best and rarely provide a significant survival benefit, and side effects from further treatments may potentially impair quality of life. In spite of aggressive chemotherapeutic treatments, only 5% 5- year survival rates are reported. Taken together, the clinical benefit of systemic chemotherapy is still frustrating.
On the other hand, several reports and clinical trials, including a phase-III trial, have demonstrated that specific cellular immunotherapy using dendritic cells is capable of inducing a clinical antitumor response in GBM IV and other malignant brain tumors, with sometimes prolongation of the overall survival. This could also be shown by our own observations (see survival curves). A dendritic cell therapy after surgery and radio-chemotherapy is leading to a clear improvement in the overall median survival. The longest overall survival for those GBM IV patients is 140 months after primary diagnosis. Even upon recurrence after failure of standard therapy, dendritic cell therapy can prolong the median survival. Comparable results are reported for other malignant brain tumors, like anaplastic astrocytoma or oligodendroglioma WHO III.
Green: survival curve for patients with de novo GBM IV who start with the DC therapy upon recurrence, median overall survival: 19 months.
Blue: survival curve for patients with de novo GBM IV, who start with the DC therapy after surgery and radio-chemotherapy, median overall survival: 31 months.