Research in neuro-oncology

The scientific focus of the Laboratory for Molecular Neuro-Oncology at the Department of Neurology is on tumor immunology and immunotherapy, treatment resistance, and the development of new therapies for patients with brain tumors.

The laboratory is located in the Haldenbach Building at the Department of Neurology of the University Hospital Zurich at Frauenklinikstrasse 26, 8091 Zurich. It is jointly led by Prof. Dr. M. Weller, Prof. Dr. P. Roth, and PD Dr. Dr. T. Weiss with the support of J. Friesen and T. Pesch (laboratory management) and K. Weissbecker (administration).

Prof. Dr. M. Weller expenses the mechanism of action of setotonin modulators, which have been identified (in cooperation with B. Snijder, Botnar Institute of Immune Engineering Basel) as a new therapeutic approach for glioblastomas using ex vivo drug sensitivity profiling (pharmacoscopy), together with S. Dahmani, J. Friesen, and T. Pesch; the significance of steroid signaling pathways, together with L. König and J. Friesen; and the tumorigenic function of telomerase, together with Y. Abdel Moneim, J. Friesen and T. Pesch.

Prof. Dr. P. Roth headed the clinical research focus “ImmunoCure” until the end of 2024, in which new immunotherapeutic treatment approaches were developed in interdisciplinary collaboration, including the characterization of chimeric antigen receptor (CAR) T cells as an approach to targeted immunotherapy for brain tumors. Dr. M. Mastall, Dr. A. Eisele, and doctoral students M. Soballa and S. Stanclik worked on projects to develop new immunotherapeutic treatment approaches for gliomas. Together with P. Will, P. Roth is also investigating epigenetic and immunological factors that contribute to long-term survival in patients with glioblastoma. P. Roth also heads the Neuroimmunology Department at the clinic. As part of a PhD project, L. Casty is working on cellular immunotherapies that are being investigated in preclinical models of inflammatory CNS diseases.

PD Dr. Dr. T. Weiss is developing new (immuno)therapeutic approaches for the treatment of gliomas and brain metastases in mouse models and early clinical trials. He is also developing new approaches for the non-invasive early diagnosis and monitoring of brain tumors in the blood and cerebrospinal fluid of patients (liquid biopsies). In this context, he is investigating tumor-specific antibody-based therapies (together with S. Guenther) as well as adoptive cell therapies with genetically modified T/NK cells and macrophage-based therapies (together with M. Bouzereau and C. DellAnna Misurale). Furthermore, he uses innovative methods for the molecular and functional characterization of tumor tissues based on mass spectrometry for high-throughput analysis of proteins (together with A. Brzobohata and Y. Zhang) and automated microscopy and computer-assisted image analysis (in collaboration with B. Snijder, Botnar Institute of Immune Engineering Basel). Together with A. Buck and I. Sakic, he uses pharmacological and genetic high-throughput screens (CRISPR screens) to identify new therapeutic approaches.

The RCAS/tv-a gene transfer system is used to further develop syngeneic mouse models of gliomas and meningiomas whose histopathological structure, microenvironment, and molecular properties resemble those of human tumors. S. Marashli und J. Uriach bearbeiten Projekte, die diese Tumormodelle nutzen, um anti-glutamaterge Therapiestrategien zu entwickeln. They are co-supervised by PD Dr. H.G. Wirsching, who has been head of the Department of Neurology at the Cantonal Hospital in Winterthur since the end of 2024.

In cooperation with the Department of Neurosurgery (Prof. Dr. L. Regli, PD Dr. C. Serra, Dr. K. Akeret, Dr. F. Vasella, Dr. S. Voglis), a tumor bank has been established for molecular biological and immunological investigations as well as for the isolation and characterization of glioma stem cells. There is also close collaboration with the group of Prof. Dr. M. Neidert at the Cantonal Hospital of St. Gallen In addition to supervising joint doctoral students on third-party funded projects on T cell antigen identification in brain tumors, the collaboration also includes cooperation on several ongoing clinical trials.

In cooperation with the Departments of for Medical Oncology and Hematolgoy (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 are being conducted on the pathogenesis and biology of metastases of the central nervous system.

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

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 projects in clinical, pathological, and molecular patient-oriented research are being carried out. Our group is part of the GLASS consortium and is working on characterizing the progression of low-grade gliomas (Dr. Dr. T. Weiss).

Our group was or is being funded by the Brain Tumor Funders Collaborative in the US, 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 CCCZ Lighthouse Program, 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, the Geistlich-Stucki Foundation, the EU’s Eurostars program, and the German Research Foundation. It carries out collaborative projects with the following companies: Lundbeck (Zug), MSD (Lucerne), Novartis (Basel), 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

  • Understanding the evolution of brain metastasis from solid tumors under therapeutic pressure
    Le Rhun (Oncology) und H. Moch (Pathology)
    Sophien-Stiftung
    10/2020 – 12/2025
  • Optimal Synergistic Immunotherapy Strategy
    Eurostars / Horizon Europe
    Roth
    7/2022 – 12/2025
  • Tissue and liquid biomarkers in the IT-IO study of intrathecal double immune checkpoint inhibition for patients with leptomeningeal metastasis from non-small cell lung cancer or melanoma.
    Weller und E. Le Rhun (Oncology)
    Foundation for Applied Cancer Research
    01/2024 – 12/2025
  • Parallel targeting of tumor cells and the tumor microenvironment as an innovative CAR T cell strategy against gliomas.
    Roth
    Swiss National Science Foundation
    9/2023 – 8/2026
  • Genomic, proteomic and microenvironmental heterogeneity between brain metastases and primary tumors in patients with metastatic breast cancer
    Le Rhun (Oncology)
    Promedica-Foundation
    10/2021 – 9/2026
  • mRNA-based CAR immune cells against glioblastoma
    Weiss
    Swissbridge
    10/2024 – 10/2026
  • Spatially resolved functional drug & immunotherapy profiling for novel combination therapies against glioblastoma
    Weiss
    Oncosuisse
    12/2023 – 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)
    G. Wirsching (Neurology)
    Swiss National Science Foundation
    01/2022 – 12/2026
  • Genome-wide CRISPR-knockout screen for identification of immunomodulatory genes in glioblastoma
    Weller
    San Salvatore Foundation
    1/2024 – 12/2026
  • IMMUNO-CAR ZURICH: Precision Immune-Oncology by Engineering Immune Cells to Treat Cancer
    Weiss
    CCCZ Lighthouse Project
    01/2024 – 12/2026
  • Development of antibody-cytokine conjugates (immunocytokines) for the treatment of isocitrate dehydrogenase (IDH) mutant grade II-IV gliomas
    Weiss
    EUROSTARS
    03/2024 – 02/2027
  • Vortioxetine against glioblastoma: drug repurposing meets cancer neuroscience
    Weller
    Swiss Cancer League (Oncosuisse)
    10/2024 – 12/2027
  • Spatially informed treatment of glioblastoma
    G. Wirsching (Neurology)
    Swiss National Science Foundation
    01/2024 – 12/2027
  • 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
    Weiss
    Bridge Discovery
    02/2024 – 02/2028
  • Long-term survival in patients with glioblastoma
    P. Will (Neurology)
    Geistlich-Stucki-Stiftung
    10/2025 – 09/2028

 

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
    Study on the safety and effectiveness of the tumor-targeting 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
    Current state: enrolment on hold
    Contact: tobias.weiss@usz.ch
  • Gliostar, phase I/II
    Study on the safety and effectiveness of the antibody-cytokine fusion protein L19TNF in combination with lomustine in patients with glioblastoma in the first relapse
    Sponsor: Philogen
    PI: Dr. Dr. T. Weiss
    Current state: closed for enrolment
    Contact: tobias.weiss@usz.ch
  • BI 1438-0003, phase 1b
    Phase Ib open-label, multi-center, dose-escalation trial of BI 764532 given as monotherapy administered by repeated intravenous infusions in patients with glioma expressing DLL3
    PI: Prof. Dr. P. Roth
    Current state: open
    Contact: patrick.roth@usz.ch
  • Debio 0123-GBM-105, phase 1/b
    Phase 1/2 open-label study of Debio 0123 in combination with temozolomide in adult participants with recurrent or progressive glioblastoma and of Debio 0123 in combination with temozolomide and radiotherapy in adult participants with newly diagnosed glioblastoma
    PI: Prof. Dr. P. Roth
    Current state: open
    Contact: patrick.roth@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 glioblastoma in relapse
    Sponsor: Nerviano Medical Sciences
    PI: n.a.
    Current state: open
    Contact: Michael.weller@usz.ch
  • EF-41, phase III
    A phase 3 study of Optune with temozolomide and pembrolizumab in glioblastoma
    Sponsor: Novocure
    PI: n.a.
    Current state: open
    Contact: Michael.weller@usz.ch
  • GBM AGILE, phase II/III
    Global Adaptive Trial Master Protocol: International study with a treatment 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
    Current state: enrolment on hold
    Contact: michael.weller@usz.ch
  • ReSurge, phase II
    Randomized study on the importance of resection of glioblastoma recurrences
    Sponsor: University Hospital Berne
    PI: P. Schucht, Berne
    Current state: open
    Contact: luca.regli@usz.ch
  • GLUGLIO, phase Ib/II
    Multicenter randomized study on inhibitors of the glutamate signaling pathway (gabapentin, sulfasalazine, memantine) in patients with newly diagnosed glioblastoma
    Sponsor: University of Zurich
    PI: H.-G. Wirsching
    Current state: open
    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.
    Current state: open
    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.
    Current state: open
    Contact: Michael.weller@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
    Current state: closed for enrolment
    Contact: 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: M. Weller
    Current state: open
    Contact: emilie.lerhun@usz.ch

Completed PhD and MD/PhD projects

Die abgeschlossenen Forschungsprojekte von PhD-Studierenden aus unserem Labor finden Sie hier aufgeführt. The relevant publications in specialist journals can be viewed via this link .

Publications

Donations

If you would like to support our scientific work in neuro-oncology with a donation, you are welcome to do so via the USZ Foundation. Under the heading “Ways to give” you will find all information on the subject of support, as well as the contact persons. Please enter “Neuro-Oncology” as the purpose of funding.

USZ Foundation