Research > Focus C > Work Packages C03
Summary
The project develops methods for in vivo imaging of cellular and subcellular dynamics of the inflammatory glioma microenvironment (innate and adaptive immune responses) and its changes during immunotherapy by MRI and optical methods. This will lead to imaging signatures of glioma response and resistance towards immunotherapies, aid preclinical immunotherapy development and ultimately improve clinical trial monitoring. The visual abstract below shows the aims and planned tasks of the work package.
Based on the findings of work package C03 there was a shift in reserach focus for the second funding period. The follow-up project will analyze imaging characteristics of H3K27M-mutant gliomas and biomarkers for response to neoepitope-specific adoptive T cells therapies in orthotopic patient-derived tumor models and clinical cohorts of adult patients with H3K27M-mutant gliomas (B06).
Task 1
Develop imaging signatures of response and resistance assessed by MRI and optical methods
Steps / Workflow
- Correlative MRI and 2- photon microscopy for imaging the tumor microenvironment
- Multi-modality innate immune cell tracking in check point inhibition (and other immunotherapies) using nanoparticle MRI
- Imaging biomarker discovery
- Radiomics
Task 2
Tracking of T-cell dynamics in adoptive transfer and tumor antigen vaccination models
Steps / Workflow
- T-cell labeling by NP
- T-cell tracking in adoptive T-cell transfer and peptide vaccination models
- MRI and optical assessment of T-cell dynamics and tumor responses in the same animal
Task 3
Generation of a bimodal nanoparticle for modulating the tumor micro-environment and imaging
Steps / Workflow
- Synthesis and in vitro characterization of bimodal NP (iron oxide based with fluorescent tag)
- in vitro functional testing on polarization effects on macrophages
- in vivo testing in immunotherapy paradigms in glioma models
Task 4
Translating successful imaging biomarkers to clinical glioma imaging and trials
Steps / Workflow
- Translation of imaging biomarkers of response and resistance for therapy monitoring
- Ultra high-field clinical MRI (7 Tesla)
- Iron oxide nanoparticle imaging (e.g. ferumoxytol)
- Radiomics
PRINCIPLE INVESTIGATOR
BRECKWOLDT, MICHAEL, DR. MED., PH.D
Clinical Resident / Post Doc
University Hospital Heidelberg, Department of Neuroradiology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany