Immunotherapy against Brain Tumors

The use of immunotherapy to attack tumors is a promising new approach to cancer treatment. The Clinical Research Priority Program (CRPP) ImmunoCure intends to develop immunotherapeutic strategies for brain tumors. We talked with Patrick Roth of the Department of Neurology and the Brain Tumor Center, University Hospital Zurich, about the CRPP’s plans.

ZNZ News: What are the aims of the CRPP ImmunoCure?
Patrick Roth:
ImmunoCure is a consortium of research groups aiming at the development of novel immuno-therapeutic strategies for various types of cancer including brain tumors. A major focus of the program is the development of CAR T cells (genetically engineered immune cells) as well as bispecific antibody constructs which can be used as therapeutic weapons against tumors.

What are the principles of CAR T cell therapy?
Chimeric antigen receptors (CAR) are recombinant proteins binding to a specific antigen that is ideally exclusively expressed on a tumor cell. T cells from a patient are engineered to express a CAR which shall allow them to become activated immediately when they encounter and recognize a tumor cell. These engineered cells are then administered back to the patient. This strategy has led to impressive therapeutic activity in patients with lymphomas and such CAR T cells are already in clinical use at the University Hospital Zurich since 2019, although not for patients with brain tumors.

Has CAR T cell therapy already been used on brain tumors?
There is a strong interest in using CAR T cells also for the treatment of brain tumors. Several research groups are working in this field and early clinical trials have already been performed in the US. However, the clinical development is still at an early stage.

What are the challenges of targeting brain tumors?
Treatment of solid tumors such as brain tumors is more challenging for a T cell- or antibody-based therapy than lymphomas, just because of their accessibility. Our research aims at improving the therapeutic activity of these new immunotherapeutic strategies but focuses also on their safety, which is of particular importance in the CNS.

What triggered the start of the CRPP?
Several groups at the University Hospital, the University and ETH Zurich have a strong focus on immunotherapy. The CRPP now provides a unique opportunity to join forces and synergistically develop a “targeted therapy development and technology immunotherapeutic platform” for the treatment of cancer in Zurich. Two lead disease focus programs have been defined, one on brain tumors and one on hematologic stem cell malignancies. These programs will be used to create a platform on which treatments for other tumor types can be based.

Which groups contribute to the program?
Two groups from the Department of Medical Oncology and Hematology (Prof. Markus Manz, Prof. Cesar Nombiela-Arieta) have a focus on hematological malignancies as well as novel imaging techniques. Research groups from the Institute of Experimental Immunology (Prof. Burkhard Becher, Prof. Christian Münz) are focusing on various aspects of the immunology of the central nervous system. At the Department of Neurology and Brain Tumor Center (Prof. Michael Weller and myself) we have long-lasting expertise in brain tumor research and the development of novel immunotherapeutic approaches against these tumors. Finally, the group of Prof. Dario Neri from ETH Zurich provides additional expertise in antibody generation and modification.

What do you hope to achieve in 5 years’ time within the scope of the CRPP?
We will investigate the therapeutic activity as well as safety profiles of CAR T cells and other antibody-based immunotherapeutic strategies in appropriate preclinical models and subsequently aim at translating these treatment options to the clinical setting, e.g., in clinical phase I studies.

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Image: 3D rendered illustration of leukocytes attacking a cancer cell