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Open AccessArticle

Addition of Multimodal Immunotherapy to Combination Treatment Strategies for Children with DIPG: A Single Institution Experience

1
Immun-Onkologisches Zentrum Köln, Hohenstaufenring 30-32, 50674 Köln, Germany
2
Center for Genetic Medicine, Children’s National Health System, Washington, DC 20010, USA
3
Institute for Biomedical Sciences, The George Washington University School of Medicine and health Sciences, Washington, DC 20052, USA
4
Zyagnum, Reißstrasse 1, 64319 Pfungstadt, Germany
5
Biofocus, Berghäuser Strasse 295, 45659 Recklinghausen, Germany
6
DIPG Research Institute, Universitäts-Kinderspital Zürich; Steinwiesstrasse 75, Ch-8032 Zürich, Switzerland
*
Author to whom correspondence should be addressed.
Medicines 2020, 7(5), 29; https://doi.org/10.3390/medicines7050029
Received: 20 March 2020 / Revised: 11 May 2020 / Accepted: 13 May 2020 / Published: 19 May 2020
Background: The prognosis of children with diffuse intrinsic pontine glioma (DIPG) remains dismal despite radio- and chemotherapy or molecular-targeted therapy. Immunotherapy is a powerful and promising approach for improving the overall survival (OS) of children with DIPG. Methods: A retrospective analysis for feasibility, immune responsiveness, and OS was performed on 41 children treated in compassionate use with multimodal therapy consisting of Newcastle disease virus, hyperthermia, and autologous dendritic cell vaccines as part of an individualized combinatorial treatment approach for DIPG patients. Results: Patients were treated at diagnosis (n = 28) or at the time of progression (n = 13). In the case of 16 patients, histone H3K27M mutation was confirmed by analysis of biopsy (n = 9) or liquid biopsy (n = 9) specimens. PDL1 mRNA expression was detected in circulating tumor cells of ten patients at diagnosis. Multimodal immunotherapy was feasible as scheduled, until progression, in all patients without major toxicity. When immunotherapy was part of primary treatment, median PFS and OS were 8.4 m and 14.4 m from the time of diagnosis, respectively, with a 2-year OS of 10.7%. When immunotherapy was given at the time of progression, median PFS and OS were 6.5 m and 9.1 m, respectively. A longer OS was associated with a Th1 shift and rise in PanTum Detect test scores. Conclusions: Multimodal immunotherapy is feasible without major toxicity, and warrants further investigation as part of a combinatorial treatment approach for children diagnosed with DIPG. View Full-Text
Keywords: DIPG; multimodal immunotherapy; DC vaccination; Newcastle disease virus; hyperthermia; PanTum Detect test; Th1 shift DIPG; multimodal immunotherapy; DC vaccination; Newcastle disease virus; hyperthermia; PanTum Detect test; Th1 shift
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Van Gool, S.W.; Makalowski, J.; Bonner, E.R.; Feyen, O.; Domogalla, M.P.; Prix, L.; Schirrmacher, V.; Nazarian, J.; Stuecker, W. Addition of Multimodal Immunotherapy to Combination Treatment Strategies for Children with DIPG: A Single Institution Experience. Medicines 2020, 7, 29.

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