Therapeutic dendritic cell vaccination to improve frontline treatment of adult patients with glioblastoma multiforme (GBM) and pediatric patients with GBM and diffuse intrinsic pontine glioma (DIPG).

Based on the strong need for more targeted, tolerable and durable treatment strategies that could postpone or even prevent recurrence of disease in the most common adult malignant brain tumor, we embarked on a phase I/II clinical trial assessing frontline treatment with autologous dendritic cell (DC) vaccines loaded with glioblastoma-associated tumor antigen Wilms' tumor 1 in conjunction with conventional chemoradiation following surgery in adults with glioblastoma multiforme (GBM; NCT02649582). Childhood high-grade glioma (HGG, including GBM) and diffuse intrinsic pontine glioma (DIPG) are rare aggressive brain tumors. In the absence of a standard of care, treatment is mostly adapted from adult schedules, resulting in 5-year survival rates of less than 5% and 1% after diagnosis, respectively. With limited advanced investigational treatment options for this vulnerable patient population, we strive to extend our clinical study to the pediatric application. Ultimately working towards the clinical valorization of an adjuvant DC-based immunotherapy approach, health care evaluation is warranted. To this extent, we will include collection of patient-reported outcome on how the study therapy is experienced throughout time in the response evaluation of all study patients. As the search for biomarkers is gaining momentum in the rapidly evolving cancer immunotherapy landscape, we are also continuously expanding the screening assays on clinical patient material. The present project proposal is designed to allow completion of the intended adult GBM patient recruitment number and to extend the trial, innovating on the pediatric application of DC vaccination, health care evaluation and emerging therapeutic biomarker research. Within the context of hard-to-treat brain tumors, this study and its specific design will add a new dimension to our translational and clinical DC vaccine programs by investigating whether DC vaccination can be combined with first-line chemoradiation treatment of adult GBM and childhood HGG and DIPG patients and whether this combination leads to tumor-specific immune responses and improved survival. Exploration of patient-reported outcomes will help to improve symptom management, functional status and overall quality of life and will provide necessary information for future clinical valorization of this type of personalized medicine. In depth research on clinically valuable biomarkers will allow us to make a significant contribution to the broader (immunotherapy-oriented) scientific community.

Keywords:GLIOMA, IMMUNOTHERAPY, CLINICAL TRIAL, DENDRITIC CELLS

Disciplines:Innate immunity, Cancer therapy, Paediatrics, Biomarker discovery, Clinical trials, Biopharmaceuticals