Migliorini Denis

Prof. Denis Migliorini

Head, Neuro Oncology Unit, HUG

Assistant Professor, Department of Oncology, UNIGE

Research: Brain Tumor and Immune Cell Engineering

Tumors arising in the brain are notoriously hard to treat. Intensive research in the last decade provided in depth characterization of the molecular profile of high grade gliomas, but unfortunately no impactful novel therapies. We contributed to immune based therapies for gliomas, especially in the identification of overexpressed cell surface markers of GBM in vivo and with the development multiepitopic vaccinations using synthetic peptides. We had the opportunity to translate our research into the clinic in an early phase trial where 19 patients with newly diagnosed GBM tumors were treated with the IMA950 peptide vaccine. We were able to demonstrate safety and immunogenicity. This endeavour led to another ambitious phase I trial using a personalized vaccination approach adapted to each patient’s tumor molecular profile.

Our next endeavour is to develop improved chimeric antigen receptor (CAR)-T cell approaches for glioma for the development of successful translational programs. T-cell engineering allows the construction of cell products harboring a high-affinity single-chain fragment variable (scFv) specific for a target of interest, fused to domains necessary for full activation and costimulation. CAR-T cell therapy in the context of brain tumors is promising because glioma is a good example of how specific improvements in trafficking, persistence, and resistance to the immunosuppressive factors related to the TME will be especially critical for success of engineered cellular therapies. We are fortunate to benefit from the generous support of the ISREC Foundation and to be part of the newly formed Swiss Cancer Center Léman (SCCL) which brings together fundamental, translational and clinical cancer research experts from Geneva and Lausanne. The SCCL federates skills and ressources at the cutting edge of the fight against cancer and allows us to integrate our efforts in a wide multidisciplinary community."

Selected publications

Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors. Sostoa J, Dutoit V, Migliorini D. Int J Mol Sci. 2020 Oct 9;21(20):7449. doi: 10.3390/ijms21207449. PMID: 33050329
Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies. Parker KR, Migliorini D, Perkey E, Yost KE, Bhaduri A, Bagga P, Haris M, Wilson NE, Liu F, Gabunia K, Scholler J, Montine TJ, Bhoj VG, Reddy R, Mohan S, Maillard I, Kriegstein AR, June CH, Chang HY, Posey AD Jr, Satpathy AT. Cell. 2020 Oct 1;183(1):126-142.e17. doi: 10.1016/j.cell.2020.08.022. Epub 2020 Sep 21. PMID: 32961131
An Experimentally Defined Hypoxia Gene Signature in Glioblastoma and Its Modulation by Metformin. Calvo Tardón M, Marinari E, Migliorini D, Bes V, Tankov S, Charrier E, McKee TA, Dutoit V, Dietrich PY, Cosset E, Walker PR. Biology (Basel). 2020 Sep 2;9(9):264. doi: 10.3390/biology9090264. PMID: 32887267
Impact of Radiochemotherapy on Immune Cell Subtypes in High-Grade Glioma Patients. Dutoit V, Philippin G, Widmer V, Marinari E, Vuilleumier A, Migliorini D, Schaller K, Dietrich PY. Front Oncol. 2020 Feb 14;10:89. doi: 10.3389/fonc.2020.00089. eCollection 2020. PMID: 32117743

Researchers

Short Bio

Professor Denis Migliorini completed his MD studies and internal medicine post graduate training at the Universities of Toulouse and Strasbourg. He then moved to the University Hospitals of Geneva (HUG) where he completed his postgraduate training in medical oncology under the mentorship of Professor Pierre-Yves Dietrich. From 2015 to 2016, he successfully completed his clinical fellowship in neuro-oncology. He holds a DAS in clinical trial management from the University of Geneva (UNIGE) and became principal investigator of several early phase trials testing various anti-tumor immunotherapy approaches, including peptide vaccines for the treatment of glioblastoma. From 2017 to 2019, he performed a post-doctoral fellowship at the Center for Cellular Immunotherapies, University of Pennsylvania, in the laboratories of Professor Carl June and Professor Avery D. Posey. He trained in synthetic biology and T cell engineering, disciplines that enabled the development of CAR-T cell technology. In 2019, he was awarded the Swiss Bridge Foundation Prize in recognition of his work identifying neurotoxicity mechanisms of engineered cell therapies. Returning to Switzerland in 2020, he was appointed assistant professor at the Department of Medicine of the Faculty of Medicine of the UNIGE, and holds the ISREC Chair in Brain Tumour Immunology. At the HUG, he is an attending physician, head of the Neuro-Oncology Unit and clinical coordinator of the brain tumor biobank. Professor Migliorini is a member of the CRTOH steering committee.