Research > Focus B > Work Packages B06

Visualization and characterization of immune responses in H3K27M mutant gliomas

Summary

H3K27M-mutant gliomas exhibit a heterogeneous appearance on routine MRI with currently limited sensitivity and specificity for initial diagnosis and therapy monitoring. This 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. The visual abstract below shows the aims and planned tasks of the work package.

Task 1

Characterize the heterogeneous response towards immunotherapy by multimodality imaging

Steps / Workflow

Establish immunotherapy paradigms to modulate the TME
Perform multiparametric MRI (CEST, MR-E, NPs) and optical correlation to characterize spatial heterogeneity

Task 2

Establish and image neoepitopespecific T-cell therapies using preclinical model antigens

Steps / Workflow

Establish adoptive T cell therapy (ACT) paradigms to model antigens
Perform T cell tracking by MRI and correlated optical methods following ACT
Define imaging biomarkers of response, resistance and PsPD

Task 3

Tracking of H3K27M-reactive tTCR T-cells in HLAmatched mouse models

Steps / Workflow

Characterization of HLAmatched H3K27M in HLAmatched mouse models
Monitor tTCR T-cell therapy by imaging and immune-profiling

Task 4

Development of H3K27M-reactive CAR T-cells

Steps / Workflow

Create H3K27M-reactive CAR T-cells
Monitor CAR T-cell therapy
Identify predictors of treatment response

Task 5

Imaging biomarker discovery after H3K27M vaccination of patients

Steps / Workflow

Dissect MRI characteristics of response, resistance and PsPD to H3K27M immunotherapy
Employ advanced MRI techniques in selected Intercept H3K27M glioma patients
Define radiomic signatures and response patterns