A Living Tissue Bank of Patient-Derived Organoids From Glioma Tumors

Overview

There is a high medical need to improve treatment outcome for high-grade and low-grade glioma since no curative treatment is available. To achieve this goal, a broader understanding is needed of the causes of inter-and intratumoral heterogeneity; glioma dedifferentiation and invasion; the major determinants of malignancy and treatment failure in glioma patients. Patient-derived organoid (PDOs) of high-grade gliomas and low-grade gliomas will be used to identify the mechanisms that underlie this malignant behaviour and treatment resistance. This insight may be used to develop patient avatars to simultaneously test multiple new treatment modalities that are predictive for survival and quality of life of glioma patients.

To establish primary patient-derived three-dimensional organoid cultures from low grade and high-grade gliomas to study the mechanisms that contribute to i.e. resistance to radiotherapy and/or chemotherapy and immunotherapy, dedifferentiation, tumor invasion among others, in primary and recurrent tumors. Primary Objectives: 1. Establishment of primary patient-derived organoids (PDO) of 'de novo' and recurrent high-grade glioma (HGG) and low-grade glioma (LGG) 2. Phenotypic, genetic, epigenetic and transcriptomic characterization of HGG and LGG organoids and resemblance to the parental tumor (i.e. characterization of specific cell populations and genomic and transcriptomic profiles of PDOs) 3. Investigation of combinations of new or standard glioma systemic treatments (i.e immunotherapy, chemotherapy) with or without radiation (i.e. protons, photons). Secondary objectives 1. Establishment of co-cultures of HGG and LGG organoids with immune cells. 2. Investigation of radiation-triggered cell death mechanisms on PDOs after irradiation with photons and protons. 3. Investigation of dedifferentiation mechanisms of LGG to HGG in the context of radiation w/wo immunotherapy.

Conditions