Glioblastoma is an aggressive brain tumor. Survival rates for the condition are low, and reduce with age. While children and adolescents and young adults have 5-year relative survival rates of 19.4% and 26%, the survival rate for adults is 5.6%. It is thought that the failure of many drug-based therapeutics for the condition may be partly explained by the difficulty of drugs crossing the blood-brain barrier.
Studies show that the blood-brain barrier can be opened up via low-intensity pulsed ultrasound (LIPU) in combination with intravenous injection of microbubbles (MB)- ultrasound contrast agents that can act as echo-enhancers and therapeutic agents. Research shows that the technique is well-tolerated and effectively disrupts the blood-brain barrier in patients with recurrent glioblastoma.
In the current study, researchers investigated whether LIPU/ MB could increase the efficacy of a novel immunotherapy treatment combination- chemotherapy drug doxorubicin and immune checkpoint blockade antibodies- for treating glioblastoma.
To do so, they observed the effects of the drug combination on four patients with recurrent glioblastoma alongside mouse models of the condition. Patients were fitted with a skull-implantable ultrasound device.
Ultimately, the new approach increased the concentration of doxorubicin by 2 and 3.9 fold in human and murine brains two days following sonication. It also led to a 6-fold and 2-fold increase in PD-1 blocking antibodies (aPD-1) concentrations in mouse brains and certain areas of human brains.
“This is the first report in humans where an ultrasound device has been used to deliver drugs and antibodies to glioblastoma to change the immune system, so it can recognize and attack the brain cancer,” said co-corresponding author Dr. Adam Sonabend, Associate Professor of Neurological Surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurosurgeon, in a press release.
“This could be a major advance for the treatment of glioblastoma, which has been a frustratingly difficult cancer to treat, in part due to poor penetration of circulating drugs and antibodies into the brain,” he added.
The findings form the basis of a new clinical trial launched at Northwestern. The trial will use ultrasound to deliver the immunotherapy for glioblastoma, and aims to enroll 10 participants initially to determine its safety, followed by 15 additional participants to assess whether it can prolong survival.
Sources: Neuroscience News, Nature Communications