Neuro-oncology

Content

 

Introduction

The Laboratory of Molecular Neurooncology is located at the Department of Neurology of the University Hospital Zurich (Frauenklinikstrasse 26, CH-8091 Zurich). The Laboratory is led by Prof. Dr. M. Weller together with PD Dr. P. Roth, and Dr. M. Silginer (organisational chart).

Major research areas of the laboratory include cancer immunology, mechanisms of migration, invasion and angiogenesis, and resistance to therapy.

Major goals of our cancer immunology research include the characterization of immunological characteristics of glioma cells, in particular the putative tumor stem cells. We are also exploring transforming growth factor beta (TGF-beta)-mediated pathways and TGF-beta-targeting therapeutics. In the framework of clinical trials, we seek to develop translational research concepts regarding the immunogenicity of glioma cells. In this context, we aim at understanding molecular mechanisms and risks of vaccination concepts in glioma and the immunogenicity of glioma cells and tumor stem cells. In addition, we perform extensive studies on the primary and acquired resistance of glioma cells to radiotherapy and chemotherapy. In cooperation with the Department of Neurosurgery (Prof. Dr. L. Regli), we currently establish a tumor bank collecting tumor tissue for histology and molecular analyses as well as for the isolation and characterization of tumor-derived glioma stem cells.

Methods employed include fluorescence tomography for in vivo imaging in our preclinical models, flow cytometry and in the framework of cooperations two-photon microscopy and positron emission tomography.

In the area of clinical neurooncology, we founded, together with the partner institutions of neuroradiology, neurosurgery, nuclear medicine, neuropathology, radiation oncology, medical oncology and pediatric neurooncology, the Brain Tumor Center Zurich at the Cancer Center Zurich in January 2012.

In cooperation with the Centers of the German Glioma Network (www.gliomnetzwerk.de), the German Consortium for Translational Cancer Research (DKTK) and the European Organization for Research and Treatment of Cancer (EORTC), we are involved in several clinical pathological molecular correlative projects looking at, e.g. prognostic and predictive value of molecular markers such as 1p 19q codeletion, MGMT promotor methylation and isocitrate dehydrogenase mutations in different glioma entities and long-time survival in glioblastoma.
  
The laboratory has been supported by the Brain Tumor Funder Collaborative, Swiss National Science Foundation, Oncosuisse, the Zurich Cancer League, the Wilhelm Sander-Foundation, the EMDO Foundation, the Hartmann-Müller Foundation and the Koetser Foundation and performs cooperative research projects with the pharmaceutical companies Abbvie (North Chicago, Illinois), Acceleron (Cambridge, Massachussets), Actelion (Baden, Switzerland), Bayer (Leverkusen/Berlin, Deutschland), Isarna (Regensburg, Germany), Merck Serono (Darmstadt, Germany), Novocure (Jersey Isle), OGD Parma, Piqur (Basel), Roche (Basel, Switzerland) and Tragara (San Diego, California).


Address 

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


Team

Please click here to see the structural organisation chart.

You will find the list of group members on the following page.

Please click here to see the organisation chart of the laboratory teams.

 

Scientific projects

Selected scientific projects are listed in the table below. A complete overview and description of current and completed projects are listed on the website of the "Forschungsdatenbank" of the University of Zurich.


Current scientific projects

Funding source
Applicants
Titel
Duration
​​Swiss National Science Foundation (SNF)
​P. Roth
​Defining novel targets for chimeric antigen receptor (CAR)-based immunotherapy against glioblastoma​03/2017 - 02/2020
​Swiss National Science Foundation (SNF) and Sinergia
​P. Roth
​Targeting HOTAIRM1 in glioblastoma
​12/2017 - 11/2020
Klinischer Forschungs-schwerpunkt (KFSP)
​P. Roth
M.G. Manz(Hämatologie)
​ImmunoCure​01/2019 - 12/2021

​Oncosuisse / Swiss Cancer League

​P. Roth
T. Weiss

lntegrins as targets for advanced chimeric antigen receptor (CAR) T cell treatment of glioblastoma

​04/2019 - 03/2022

​OPO Foundation​H.-G. Wirsching

Digital Spatial Profiling to Map the Evolution of Intratumoral Immunologic Heterogeneity of Glioblastoma under Standard Chemoradiotherapy

01/2019 - 12/2019

Desirée and Niels Yde Foundation

H.-G. Wirsching

Evolution of the genomic-immunologic landscape of glioblastoma under chemoradiotherapy

01/2019 - 12/2021

 

Current clinical trials

Title
Principal Investi­gator
Indication
Contact in Zurich
Status
​EORTC 1608-BTG, Phase Ib

TGO2 in elderly newly diagnosed or adult relapsed patients with anaplastic astrocytoma or glioblastoma
​Prof. Dr. M. Weller,
Zürich
​Newly diagnosed anaplastic astrocytoma or glioblastoma (>65 years)

Recurrent anaplastic astrocytoma or glioblastoma (>18 years)
​PD Dr. P. Roth​recruiting
CheckMate 548, phase III

Study of temozolomide plus radiation therapy with nivolumab or placebo, for newly diagnosed patients with glioblastoma
​Bristol-Myers Squibb,
PD Dr. P. Roth
​Newly diagnosed glioblastoma, methylated MGMT promotor​PD Dr. P. Roth
completed
EORTC-1709-BTG, Phase III

Multicenter study of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma
​PD Dr. P. Roth​Newly diagnosed glioblastoma​PD Dr. P. Roth​recruiting
Gliomoon, phase I/II

A study to evaluate the safety and efficacy of the tumor-targeting human antibody-cytokine fusion protein L19TNF in patients with IDH wildtype WHO grade III /IV glioma at first relapse

​Dr. T. Weiss
​IDH wildtype WHO grade III /

IV glioma at first relapse

​Dr. T. Weiss​recruiting
CDI-CS-003, phase I/IIa

BAL101553 in patients with advanced solid tumors or recurrent glioblastoma
​Basilea,
PD Dr. P. Roth  
​Recurrent glioblastoma​​PD Dr. P. Roth​recruiting
BGB-290-104, phase I/IIa

Multicenter study to assess the safety, tolerability
and efficacy of BGB-290 in combination with radiation
therapy and/or temozolomide in patients with newly diagnosed
or recurrent glioblastoma
​BeiGene,
Prof. Dr. M. Weller 
​Newly diagnosed glioblastoma, unmethylated MGMT promotor or recurrent glioblastoma
​Prof. Dr. M. Weller
Dr. K. Seystahl
Dr. H.G. Wirsching
​recruiting
PQR309-005, phase II

Open-label, non-randomized, two-stage study to evaluate the efficacy and safety of PQR309 in patients with progressive primary CNS lymphoms
​Prof. Dr. M. Weller,
Zürich
​Recurrent primary CNS lymphoma
​Prof. Dr. M. Weller
Dr. D. Gramatzki
​recruiting
PCNSL01, phase II

Pembrolizumab for recurrent primary CNS lymphoma
​PD Dr. P. Roth
​Recurrent primary CNS lymphoma
​PD Dr. P. Roth
​recruiting

 

Completed PhD research projects

Completed projects of PhD students of our laboratory are listed below. Related publications can be found by the following link

Name
 
Projekt
Start
End
SilginerManuelaIntegrin inhibition interferes with TGF-beta signaling in malignant glioma cells2010-012013-10
AhmadMushfikaHow stem-like are sphere cultures from long-term cancer cell lines?2010-082013-11
CodoPaulaGrowth and differentiation factor (GDF)-15, microRNA and the immunophenotype of glioblastoma2011-022014-09
StojcevaNinaTMZ resistance in glioblastoma2012-012015-06
ShanmugarajanKrishnanModulation of cerebral endothelial cell function by Glioma-Derived factors2012-102016-04
SchroederJudithThe Role of TGF-β Coreceptors in Glioblastoma2012-102015-09
ManganiDavideCo-inhibition of the TGF-β and VEGF pathways in glioblastoma2013-012017-06
PapaEleannaCrosstalk between the Met and TGF-β pathways in glioblastoma2013-012017-06
PapachristodoulouAlexandrosFocused ultrasound-mediated delivery of encapsulated MGMT antagonists for the treatment of temozolomide-resistant glioblastoma2013-012017-05
VenturaElisaExtracellular control of TGF-beta signaling in glioblastoma2013-012017-06
von AchenbachCarolineGrowth factor signalling in glioblastoma2015-022018-09
LohmannBirtheModulation of glioblastoma biology by type I interferons2015-012018-09
WeissTobiasCharacterisation and exploitation of the NKG2D system in glioblastoma2015-092019-04

Publications

Please follow the link to the detailed list of publications here.

Links


 


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