Background
Glioblastoma (GBM) is the most frequent, aggressive and lethal brain tumour. It has a universally fatal prognosis and despite significant efforts clinicians are as yet unable to offer GBM patients a curative therapy. Effective precision medicine therapies are thus urgently required. The GBM tumour microenvironment (TME) consists of various cell types including the cancer cells themselves, but also non-cancerous cells such as normal brain cells (glial cells and microglia), vascular cells and different types of immune cells. The interactions between all of these cells is known to contribute to the intractability of this disease. Overall, the project seeks to identify a new TME-targeting platform for GBM brain tumours.
The GLIORESOLVE project will exploit this urgent clinical need for novel precision medicine strategies to train a new generation of highly skilled doctoral candidates (PhD candidates) in the neuro-oncology, immune-oncology and digital pathology/spatial ‘omics’ domain.
The consortium comprises 21 international organisations and brings together leading academics, clinicians, private sector and not-for-profit partners from 10 countries. It incorporates disruptive research methods including multi-omics, ex-vivo ‘tumour-on-a-chip’ assay development, computational modelling and systems biology.
Glioresolve Research Activities
There are two scientific work packages (WP) in GLIORESOLVE: GlioImmune and GlioDiscover.
GlioImmune (WP1) aims to implement state-of-the art technologies to identify and refine viable, subtype-specific combinatorial immunotherapy approaches to target GBM. Six PhD students will work on this WP and will study rational combinations of immune therapies and will evaluate intrinsic patterns of response and resistance using clinical, preclinical and in silico data.
WP1 Projects:
Project 1: Development of optimized oncolytic virus therapy for GBM TME subtypes
Beneficiaries: Erasmus MC, Mimetas BV
Associated Partner: Brigham and Women’s Hospital
Project 2: Evaluation of ultrasound-induced TME-subtype modulation in combination with ICIs in GBM
Beneficiaries: ICM Institute for Brain and Spinal Cord, RCSI
Associated Partner: Carthera, Sorbonne Université
Project 3: Targeting the Treg – macrophage axis to promote immune stimulation and tertiary lymphoid structure formation in GBM TME subtypes
Beneficiaries: VIB, KUL, Bayer AG
Project 4: Targetability of GBM TME subtype – specific T cell and GBM associated endothelial cell interactome
Beneficiary: Medical Faculty Mannheim - University of Heidelberg
Associated Partners: Miltenyi Biotec B.V. & Co. KG
Project 5: Patient-derived screening platform for probing personalized immunotherapies in TME-based GBM subtypes
Beneficiaries: Luxembourg Institute of Health
Associated Partners: Laboratoire national de santé, Oslo University Hospital, Univerosty of Luxembourg
Project 6: Establishment of GBM TME subtypes-on-chip models
Beneficiaries: Mimetas BV, Erasmus MC,
GlioDiscover (WP2) focuses on the discovery and interrogation of (non-immune) TME-targeting therapies. Four PhD students will interrogate novel therapeutics using advanced models and will employ gene regulatory networks and multi’ omics to determine mechanisms and biomarkers of resistance across TME subtypes.
WP2 Projects:
Project 7: Identification of novel TME subtype-specific treatments for GBM
Beneficiaries: RCSI, Bayer AG
Project 8: Modelling therapeutic resistance in GBM TME subtypes using multiomics computational models
Beneficiaries: GeneXplain GmbH, RCSI
Project 9: Mapping the therapeutic potential of Ag5 and its effects on the TME using a multi-omics approach in GBM patient derived models
Beneficiary: KU Leuven
Associated Partner: Arjuna Therapeutics
Project 10: Novel combination approaches of targeted alpha therapies in GBM TME subtypes
Beneficiaries: Bayer AG, RCSI
Associated Partner: Charité – Universitätsmedizin