Research in neuro-oncology

The scientific focus of the Laboratory for Molecular Neuro-Oncology at the Department of Neurology is on the fields of tumor immunology and immunotherapy, therapy resistance and the development of new therapies for brain tumor diseases.

The laboratory is located in the Haldenbach Building at the Department of Neurology of the University Hospital Zurich at Frauenklinikstrasse 26, 8091 Zurich and is headed by Prof. Dr. M. Weller with the support of J. Friesen and T. Pesch (laboratory management) and K. Weissbecker (administration). Prof. Dr. P. Roth, Dr. Dr. T. Weiss and PD Dr. H.-G. Wirsching have obtained independent funding and lead junior research groups.

Prof. Dr. P. Roth heads the clinical research focus “ImmunoCure“, in which new immunotherapeutic treatment approaches are developed in interdisciplinary collaboration and, among other things, Chimeric Antigen Receptor (CAR) T cells are characterized as an approach to targeted immunotherapy for brain tumours. Dr. M. Mastall, Dr. A. Eisele and the doctoral students M. Soballa and S. Stanclik are working on projects in which new immunotherapeutic treatment approaches for gliomas are being developed. P. Roth is also head of the clinic’s neuro-immunology department.

Dr. Dr. T. Weiss is developing new immunotherapeutic approaches for the treatment of gliomas and brain metastases in mouse models and early clinical studies. He is also developing new approaches for the non-invasive early diagnosis and monitoring of brain tumors in patients’ blood (‘liquid biopsies’). Together with T. Look and M. Bouzereau, he is investigating tumor-specific antibody-based therapies as well as adoptive cell therapies with genetically modified T/NK cells and, together with M. Sun, macrophage-based therapies. Furthermore, he uses innovative methods for molecular and functional characterization of tumor tissues based on mass spectrometry for high-throughput analysis of proteins (together with A. Brzobohata, M. Bühler and Y. Zhang) and automated microscopy and computer-assisted image analysis (in collaboration with B. Snijder ETH Zurich). Together with A. Buck and I. Sakic, he uses pharmacological and genetic high-throughput screens (‘CRISPR screens’) to identify new therapeutic approaches.

PD Dr. H.-G. Wirsching uses the RCAS/tv-a gene transfer system to further develop syngeneic mouse models of gliomas and meningiomas whose histopathological structure, microenvironment and molecular properties are similar to human tumors. S. Marashli, V. Moisoiu and J. Uriach are working on projects that use these tumor models to investigate possible gene functions and identify new therapeutic targets. In addition, these models are used to investigate the effects of epilepsy and anticonvulsants on tumor growth. One focus in the application of these models is on gene expression analyses with spatial and cell type-specific resolution.

In cooperation with the Department of Neurosurgery (Prof. Dr. L. Regli, Dr. Dr. E. Le Rhun, Dr. F. Vasella), a tumor bank for molecular biological and immunological studies as well as for the isolation and characterization of glioma stem cells was established.

In cooperation with the Departments of Medical Oncology and Oncology (PD Dr. Dr. E. Le Rhun), Neurosurgery (Prof. Dr. L. Regli) and Radiation Oncology (Prof. Dr. M. Guckenberger) and the Institute of Pathology (Prof. Dr. H. Moch), several externally funded projects on the pathogenesis and biology of metastases of the central nervous system are being carried out.

In the field of clinical neuro-oncology, the Brain Tumor Center Zurich was founded at the Comprehensive Cancer Center Zurich (CCCZ) in January 2012 together with the partner institutions of neuroradiology, neurosurgery, neuropathology, radiation oncology, oncology, nuclear medicine and pediatric neuro-oncology in Zurich. The extensive clinical studies (see below) are comprehensively supervised by three study nurses, M. Adorjani, V- Gbaler and C. Keding, provide comprehensive support.

PD Dr. D. Gramatzki, Dr. A. Eisele and Dr. Y. Abdel-Moneim are conducting population-based studies on glioma disease in the Canton of Zurich. In cooperation with the centers of the German Glioma Network (coordination: PD Dr. D. Gramatzki) and the European Organization for Research and Treatment of Cancer (EORTC) (coordination: PD Dr. Dr. E. Le Rhun), various clinical-pathological-molecular patient-related research projects are being carried out. The research group is working within the GLASS consortium on the characterization of the progression of low-grade gliomas (Dr. Dr. T. Weiss).

The working group was or is supported by the Brain Tumor Funder Collaborative of the USA, the Swiss National Science Foundation, Cancer Research Switzerland (Oncosuisse), the Zurich Cancer League, the Helmut Horten Foundation, the Wilhelm Sander Foundation, the EMDO Foundation, the OPO Foundation, the Hartmann-Müller Foundation, the Koetser Foundation, the Sophien Foundation, the San Salvatore Foundation, the Promedica Foundation, the Desirée and Niels Yde Foundation, the Foundation for Applied Cancer Research and the German Research Foundation support and carry out cooperation projects with the following companies: MSD (Lucerne), Novocure (Jersey Isle), Philogen (Siena) and Quercis (Zug).

Address

Laboratory for Molecular Neuro-Oncology
Department of Neurology
University Hospital Zurich
Frauenklinikstrasse 26
8091 Zurich

Our research team

You can find the members of the Neuro-Oncology Research Group here.

Scientific focus

A selection of our research projects is listed below. An overview of the “ImmunoCure” research focus can be viewed here.

Current third-party funded projects at the Brain Tumor Center Zurich

  • High-throughput functional profiling in complex tumor samples from patients with aggressive primary brain tumors
    T. Weiss (Neurology)
    Helmut Horten Foundation
    01/2022 – 12/2024
  • Spatially resolved functional drug & immunotherapy profiling for novel combination therapies against glioblastoma
    T. White
    Oncosuisse
    12/2023 – 12/2026
  • A CE-IVDR compliant cost-efficient and highly sensitive blood test for minimally-invasive diagnosis and monitoring of malignant brain tumors based on tumor-derived extracellular vesicles and an ultra-high throughput microfluidic device
    T. White
    Bridge Discovery
    02/2024 – 02/2028
  • Genome-wide CRISPR-knockout screen for identification of immunomodulatory genes in glioblastoma
    M. Weller
    San Salvatore Foundation
    1/2024-12/2026
  • A phase Ib/II randomized drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma (GLUGLIO)
    H.-G. Wirsching (Neurology)
    Swiss National Science Foundation
    01/2022-12/2026
  • ImmunoCure
    Clinical Research Priority Program (KFSP) at UZH
    P. Roth (Neurology) and M.G. Manz (Hematology)
    01/2019 – 12/2024
  • Treating epilepsy to treat brain cancer – repurposing of clinically approved glutamate antagonists to treat glioblastoma
    H.-G. Wirsching (Neurology)
    UZH Research Fund
    01/2022-12/2024
  • Understanding the evolution of brain metastasis from solid tumors under therapeutic pressure
    E. Le Rhun (Oncology) and H. Moch (Pathology)
    Sophia Foundation
    10/2020-12/2024
  • Genomic, proteomic and microenvironmental heterogeneity between brain metastases and primary tumors in patients with metastatic breast cancer
    E. Le Rhun (Oncology)
    Promedica Foundation
    10/2021-9/2024
  • Spatially informed treatment of glioblastoma
    H.-G. Wirsching (Neurology)
    Swiss National Science Foundation
    01/2024-12/2027

Current clinical studies at the Brain Tumor Center Zurich

If you are interested in the clinical studies listed below at the Brain Tumor Center of the USZ, we look forward to hearing from you. A tabular overview of the currently recruiting studies with the most important inclusion criteria can also be viewed here.

  • Gliosun, Phase I/II: Safety and efficacy study of the tumor-targeted human antibody-cytokine fusion protein L19TNF together with temozolomide maintenance therapy after standard radiochemotherapy in patients with newly diagnosed glioblastoma
    Sponsor: Philogen
    PI: Dr. Dr. T. Weiss
    Contact: tobias.weiss@usz.ch
  • EF-21 (TRIDENT): Randomized trial for patients with newly diagnosed glioblastoma to add OPTUNE®/TTFIELDS to standard radiochemotherapy with temozolomide
    Sponsor: Novocure
    PI: n.a.
    Contact: patrick.roth@usz.ch
  • Gliostar, Phase I/II: Safety and efficacy study of the antibody cytokine fusion protein L19TNF in combination with lomustine in patients with first relapse glioblastoma
    Sponsor: Philogen
    PI: T. Weiss
    Contact: tobias.weiss@usz.ch
  • PARPA-293-002: Phase I/II: Safety and efficacy study of the PARP inhibitor NMS-03305293 and temozolomide in patients with diffuse glioma or recurrent glioblastoma
    Sponsor: Nerviano Medical Sciences
    PI: n.a.
    Contact: dorothee.gramatzki@usz.ch
  • CNS-201: Phase II: Randomized study of the safety and efficacy of berubicin versus lomustine in patients with recurrent glioblastoma
    Sponsor: CNS Pharmaceuticals
    PI: n.a.
    Contact: michael.weller@usz.ch
  • GBM AGILE, Phase II/III: Global Adaptive Trial Master Protocol: International trial with a response-adapted randomization platform with multiple treatment arms in patients with newly diagnosed or relapsed glioblastoma
    Sponsor: Global Coalition for Adaptive Research – GCAR
    PI: T. Cloughesy, Los Angeles
    Contact: emilie.lerhun@usz.ch
  • ReSurge, Phase II: Randomized study on the value of resection of recurrent glioblastoma
    Sponsor: University Hospital Berne
    PI: P. Schucht, Berne
    Contact: luca.regli@usz.ch
  • GLUGLIO, Phase Ib/II: Multicenter randomized trial of inhibitors of the glutamate signaling pathway (gabapentin, sulfasalazine, memantine) in patients with newly diagnosed glioblastoma
    Sponsor: University of Zurich
    PI: H.-G. Wirsching)
    Contact: Hans-Georg.Wirsching@usz.ch
  • ACTION, phase III
    ONC201 for the Treatment of Newly Diagnosed H3 K27M-mutant Diffuse Glioma Following Completion of Radiotherapy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
    Sponsor: Chimerix
    PI: n.a.
    Contact: emilie.lerhun@usz.ch
  • A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Radiotherapy with or without Temozolomide and in Recurrent Glioblastoma as Single Agent
    Sponsor: Novartis
    PI: n.a.
    Contact: emilie.lerhun@usz.ch
  • IT-IO
    Intrathecal administration of anti-PD1/anti-CTLA-4 in combination with systemic combination of anti-PD1/anti-CTLA-4 in patients with NSCLC without oncogenic driver mutation or melanoma and newly diagnosed leptomeningeal metastasis: a multicentric phase I study
    Sponsor: University Hospital Zurich
    PI: E. Le Rhun
    Contact: emilie.lerhun@usz.ch
  • ETOP 19-21 USZ-STRIKE
    Immunotherapy or targeted therapy with or without stereotactic radiosurgery for patients with brain metastases from melanoma or non-small cell lung cancer
    Sponsor: University Hospital Zurich
    PI: E. Le Rhun
    Contact: emilie.lerhun@usz.ch

Completed PhD and MD/PhD projects

The completed research projects of PhD students from our laboratory are listed below. The relevant publications in specialist journals can be viewed via this link .

  • Manuela Silginer
    Integrin inhibition interferes with TGF-beta signaling in malignant glioma cells
    01/2010 – 10/2013
  • Mushfika Ahmad
    How stem-like are sphere cultures from long-term cancer cell lines?
    08/2010 – 11/2013
  • Paula Codo
    Growth and differentiation factor (GDF)-15, microRNA and the immunophenotype of glioblastoma
    02/2011 – 09/2014
  • Nina Stojceva
    TMZ resistance in glioblastoma
    01/2012 – 06/2015
  • Judith Schroeder
    The role of TGF-β coreceptors in glioblastoma
    10/2012 – 09/2015
  • Krishnan Shanmugarajan
    Modulation of cerebral endothelial cell function by glioma-derived factors
    10/2012 – 04/2016
  • Alexandros Papachristodoulou
    Focused ultrasound-mediated delivery of encapsulated MGMT antagonists for the treatment of temozolomide-resistant glioblastoma
    01/2013 – 05/2017
  • Davide Mangani
    Co-inhibition of the TGF-β and VEGF pathways in glioblastoma
    01/2013 – 06/2017
  • Eleanna Papa
    Crosstalk between the Met and TGF-β pathways in glioblastoma
    01/2013 – 06/2017
  • Elisa Ventura
    Extracellular control of TGF-beta signaling in glioblastoma
    01/2013 – 06/2017
  • Birthe Lohmann
    Modulation of glioblastoma biology by type I interferons
    01/2015 – 09/2018
  • Caroline von Achenbach
    Growth factor signaling in glioblastoma
    02/2015 – 09/2018
  • Tobias Weiss
    Characterization and exploitation of the NKG2D system in glioblastoma
    09/2015 – 04/2019
  • Lena Hänsch
    Characterizing CD317 as a novel target for chimeric antigen receptor (CAR) T cell therapy in glioblastoma
    05/2017 – 03/2021
  • Evelina Blomberg
    The role of type I IFN and PD-L1 in syngeneic mouse glioma models
    12/2017 – 07/2021
  • Clara Quijano Rubio
    The role of CD95 and CD95L interactions in human glioma-initiating cells and in syngeneic mouse glioma models
    12/2017 – 7/2021
  • Daniela Lorizio
    Targeting glioblastoma by immune checkpoint modulation and TGF-β inhibition
    1/2018 – 7/2021
  • Roxanne Lourman
    Oncogenic roles of MSH6 loss in glioblastoma
    12/2018 – 11/2022
  • Thomas Look
    Advancing immunotherapy for glioblastoma with immunocytokines
    03/2020 – 10/2023
  • Gioele Medici
    The intra-tumoral spatial heterogeneity of T cell antigens in glioblastoma: an integrated multi-omics approach
    11/2019 – 10/2023
  • Remi Weber
    CRISPR/Cas9 precision base editing and epigenetic engineering in glioma
    03/2020 – 10/2023
  • Flavio Vasella
    CRISPR/Cas-mediated base editing to correct recurrent point mutations in tumors of the central nervous system
    04/2018 – 10/2023

Donations

You can make a donation for our scientific work by simply transferring money to our neuro-oncology donation account.

Please note that “in favor of account F-86001-01-01” must be listed as a comment on the accounting allocation. If you would like to specify the actual (practical) purpose of your donation yourself, please contact us before or after the transfer. We will also be happy to issue you with a donation receipt for submission to the tax office. Please send us an informal written request with your exact address or simply give us a call.

Tel. +41 44 255 55 00