Pediatric glioblastoma multiforme (GBM) models for immunotherapy testing: Incorporating models of the tumour immune microenvironment and the blood-brain-barrier (BBB).

Abstract

Pediatric Glioblastoma Multiforme (GBM), while not as common as adult GBM, exhibits poor prognosis despite the application of many conventional cancer treatment approaches. Cancer immunotherapy, including cancer vaccines, adoptive T-cell therapy, oncolytic virotherapy and checkpoint inhibitor therapy, has showcased promising treatment effects for many solid tumours and is currently explored for pediatric GBM treatment, as well. Patient response to immunotherapy is closely related to the composition of the tumour microenvironment and its immune components. Therefore, preclinical tumour models incorporating constituents of the tumour immune microenvironment (TIME) are essential as platforms for testing immunotherapy. For the testing and development of immunotherapeutic and other drug treatments for brain tumours, the treatment needs to cross the Blood-Brain-Barrier (BBB). In-vitro models of the BBB can be used to assess BBB permeability for a specific drug. Here we present an overview of immunotherapeutic options for pediatric GBM, in the stage of clinical-trial research, and analyze in-vitro and in-vivo mouse models as well as in-vitro BBB models for the testing of current or future immunotherapy against pediatric GBM. In-vitro 3D organoid models of pediatric GBM are an already-established model, showing early signs of promising results as a platform for adoptive T-cell therapy testing, with future steps entailing TIME representation for patient-specific immunotherapy testing.