RT Journal Article
SR Electronic
T1 Adjuvant Wilms’ tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e077613
DO 10.1136/bmjopen-2023-077613
VO 14
IS 3
A1 Van Genechten, Toon
A1 De Laere, Maxime
A1 Van den Bossche, Jolien
A1 Stein, Barbara
A1 De Rycke, kim
A1 Deschepper, Caroline
A1 Hazes, Katja
A1 Peeters, Renke
A1 Couttenye, Marie-Madeleine
A1 Van De Walle, Katrien
A1 Roelant, Ella
A1 Maes, Sabine
A1 Vanden Bossche, Stephanie
A1 Dekeyzer, Sven
A1 Huizing, Manon
A1 Caluwaert, Kim
A1 Nijs, Griet
A1 Cools, Nathalie
A1 Verlooy, Joris
A1 Norga, Koen
A1 Verhulst, Stijn
A1 Anguille, Sebastien
A1 Berneman, Zwi
A1 Lion, Eva
YR 2024
UL http://bmjopen.bmj.com/content/14/3/e077613.abstract
AB Introduction Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms’ tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG.Methods and analysis 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8–10×106 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150–200 mg/m2 on days 1–5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life.Ethics and dissemination The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences.Trial registration number NCT04911621Data will not be freely accessible, but will be saved and made available for clinical reseachers upon request.