An interdisciplinary research team from Zurich has designed an immunocytokine which has striking anti-cancer activity for glioblastoma. The paper published in the journal Science Translational Medicine describes a new technique and how well it worked when tested with mouse models and in patients in a pilot trial.
Glioblastoma is the most aggressive primary brain tumor and treatment options are limited. Despite multimodal treatment, the prognosis remains poor with a median overall survival of approximately 16 months. Finding novel therapeutic strategies is therefore crucial. We explored the activity of antibody-cytokine fusion constructs, also known as immunocytokines, which allow for a targeted delivery of proinflammatory cytokines to the tumor site in the brain.
Together with the group of Prof. Dario Neri from ETH Zurich who developed these molecules, we tested the anti-tumor activity of several immunocytokines in preclinical glioma models and characterized the biological effects of this approach. Based on the promising results obtained in these experiments, we initiated a clinical trial in human glioblastoma patients.
Treatment with immunocytokines prolonged the survival of glioma-bearing mice. Mechanistically, we noticed increased infiltration of tumors with immune cells and increased levels of pro-inflammatory cytokines within the tumor microenvironment. We then started a clinical trial for human glioblastoma patients and observed that some of the pharmacodynamic findings seen in mice were also present in human patients. Immunocytokines may therefore be promising drugs for the treatment of aggressive intracranial tumors.
The development of novel immunotherapeutic strategies has been a focus of our research for many years. The successful translation of preclinical findings into the clinical settings allows us to provide patients access to novel therapeutic options. The first clinical trial will complete patient enrolment and a further study has already been initiated. In this second trial, the administration of immunocytokines will be combined with conventional treatment modalities such as radiotherapy and alkylating chemotherapy. Together with several other projects, the ongoing preclinical and clinical development of immunocytokines is part of the Clinical Research Priority Program (CRPP) “ImmunoCure”, which is funded by the University of Zurich.
By: Patrick Roth, Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich
Reference: Immunocytokines are a promising immunotherapeutic approach against glioblastoma. Weiss T, Puca E, Silginer M, Hemmerle T, Pazahr S, Bink A, Weller M, Neri D, Roth P. Sci Transl Med 2020 Oct; 12(564): eabb2311 Article
Other useful links: Clinical Research Priority Program ImmunoCure