How do immunotherapies get to brain tumors?
People who are diagnosed with glioblastoma usually only have a few months to live. One reason why this type of malignant tumor is so hard to treat is because drugs – and even the contrast agents necessary for an MRI diagnosis – can only partially reach it. This is because the brain and spinal cord are separated from the bloodstream by the brain-blood barrier. The barrier is both a blessing and a curse: Although it protects us by keeping out foreign substances, pathogens, and toxic metabolites, it is also an obstacle to effective drug therapies for brain diseases.
This is the case for patients with glioblastoma. Immunotherapies like the checkpoint inhibitor ipilimumab can fight some tumors very successfully. It allows people with malignant melanoma, for instance, to live substantially longer than they otherwise would. In addition, an increasing number of findings show that similar immunotherapies can be effective against brain metastases. However, says Dzaye, “the clinical studies we are currently carrying out within the Brain Cancer Immunotherapy Program at Johns Hopkins University have shown that patients with primary brain tumors – particularly those with glioblastoma – almost never respond to these immunotherapies.”
Dzaye, a neuroscientist and radiologist, hopes to change that. To this end, he has successfully attracted funding from the Else Kröner-Fresenius-Stiftung. The €220,000 Else Kröner Memorial Grant will allow him to spend three years working on treatments for brain tumors as the head of an interdisciplinary research group on experimental neuroradiology at Charité, in collaboration with Professor Helmut Kettenmann of the Max Delbrück Center for Molecular Medicine (MDC).
Dzaye and his team are planning to use two approaches to make glioblastoma tumors more vulnerable: They want to activate dendritic cells, which can “digest” cancer cells and then display fragments on their surface to alert the immune system’s killer cells. In combination with this, they want to use specific peptides that influence the vascular muscles – because, as Dzaye has discovered, the peptides can briefly cross the blood-brain barrier. “That would allow us to get a higher concentration of medication to the brain, and we wouldn’t have to operate immediately. In other words, we’d have better noninvasive therapy options,” says Dzaye. It should also be possible to combine the peptides with other drugs, which would make the new method an attractive option for many diseases of the central nervous system, such as Parkinson’s, Alzheimer’s, and multiple sclerosis.
Dzaye currently works at the Russell H. Morgan Department of Radiology and Radiological Science at Johns Hopkins University in Baltimore, USA. Dzaye has also set up a research exchange with Baltimore, which allows him to share his contacts and expertise with interested students. Starting in February or September 2019, for example, students taking part in the exchange can spend six to eight months doing research for their projects in the United States.