Research > Focus C > Work Packages C03

Imaging immune signatures of glioma response and resistance towards immunotherapy

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.

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