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Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant by Emmanuel de Billy; Marsha Pellegrino; Domenico Orlando; Giulia Pericoli; Roberta Ferretti; Pietro Businaro; Maria Antonietta Ajmone-Cat; Sabrina Rossi; Lucia Lisa Petrilli; Nicola Maestro; Francesca Diomedi-Camassei; Marco Pezzullo; Cristiano De Stefanis; Paola Bencivenga; Alessia Palma; Rossella Rota; Francesca Del Bufalo; Luca Massimi; Gerrit Weber; Chris Jones; Andrea Carai; Simona Caruso; Biagio De Angelis; Ignazio Caruana; Concetta Quintarelli; Angela Mastronuzzi; Franco Locatelli; Maria Vinci is a Medicine article available to read on EtoBox.

What is Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant about?

## Abstract ## Background Diffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy. ## Methods Immunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function. ## Results GD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27

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Author

Emmanuel de Billy; Marsha Pellegrino; Domenico Orlando; Giulia Pericoli; Roberta Ferretti; Pietro Businaro; Maria Antonietta Ajmone-Cat; Sabrina Rossi; Lucia Lisa Petrilli; Nicola Maestro; Francesca Diomedi-Camassei; Marco Pezzullo; Cristiano De Stefanis; Paola Bencivenga; Alessia Palma; Rossella Rota; Francesca Del Bufalo; Luca Massimi; Gerrit Weber; Chris Jones; Andrea Carai; Simona Caruso; Biagio De Angelis; Ignazio Caruana; Concetta Quintarelli; Angela Mastronuzzi; Franco Locatelli; Maria Vinci

Publisher

Oxford University Press (OUP)

Published

2021

Language

EN

Field

Medicine (Health Sciences)