Research > Focus B > Work Packages B01
Summary
This project aims at identifying cellular, molecular, metabolic and imaging determinants of response and resistance to immune checkpoint blockade in glioma using preclinical animal models and studying cohorts of patients with newly diagnosed and recurrent glioma. The strategic aim is to identify cellular, molecular and imaging biomarkers, which allow to refine the use of checkpoint inhibitors in glioma treatment and to develop rational combinatorial therapies to enhance efficacy. The visual abstract below shows the aims and planned tasks of the work package.
Task 1
Define immunological determinants of response and resistance to checkpoint blockade
Steps / Workflow
Hypermututant GBM
- Relevance of mutational load in GBM for response to checkpoint blockade
- Relevant antigens and T cell receptors
- Molecular and functional profiles of tumor-associated immune cell subsets
Task 2
Unravel metabolic determinants of response and resistance to checkpoint blockade
Steps / Workflow
MALDI + microdialysis
- Metabolic biomarkers for resistance
- Response prediction, novel imaging modalities, novel druggable pathways
- Validation
Task 3
Define imaging biomarkers of response and resistance to checkpoint blockade
Steps / Workflow
MR imaging
- Iron oxide imaging to dissect role of macrophages
- Radiomic profiling
- Predictive imaging parameters
Task 4
Validate biomarkers of response and resistance to checkpoint blockade in clinical trial cohorts
Steps / Workflow
Clinical Trials
- NOA-16: glioma-specific TCRs
- AMPLIFY-NEOVAC + N2M2 Atezolizumab cohort
- MALDI + microdialysis + proteomics
- Refinement of resistance model
PRINCIPLE INVESTIGATORS
BUNSE, THERESA, NEE SCHUMACHER, DR. RER. NAT.
Post Doc
Heidelberg University, Mannheim Medical Faculty, University Hospital Mannheim, Department of Neurology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
PLATTEN, MICHAEL, PROF. DR. MED.
Chairman/Head
Heidelberg University, Mannheim Medical Faculty, Mannheim University Hospital (UMM), Department of Neurology & DKFZ, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany