Glioblastoma is one of the most deadly forms of cancer, often returning with a vengeance after surgery to remove it. Researchers at the University of Wisconsin-Madison have now developed an immunity-boosting hydrogel that can be injected into the brain after surgery to clear out remaining cancer stem cells.
The survival rates for glioblastoma are among the lowest of any cancer, with less than 5% of patients surviving five years after diagnosis. That’s largely because this brain cancer has a tendency to come back after the tumor is surgically removed, as glioma stem cells are left behind to form new tumors.
“One characteristic of glioblastoma is that the tumor cells are very aggressive, and they will infiltrate the surrounding tissues,” said Quanyin Hu, corresponding author of the study. “So the surgeon can’t clearly feel the boundaries between the tumor and the normal tissue, and you cannot remove as much as possible because all the tissues in the brain are extremely important – you certainly don’t want to remove too much.”
But a new treatment might help turn the tide. The researchers have now developed a drug-laden hydrogel that can be injected post-operation into the space left behind after a tumor is removed. There, it gets to work training the immune system to hunt down any remaining glioma stem cells.
The hydrogel contains nanoparticles that can reprogram immune cells called macrophages, which flood the site after the surgery. Frustratingly, the tumor environment can make these macrophages switch sides, so they help promote cancer growth and suppress the immune response.
The gel counters this with nanoparticles that engineer the macrophages to target CD133, a protein expressed by cancer stem cells. These fugitive cancer cells try to hide by broadcasting a signal that tells the immune system not to eat it, so the hydrogel also contains an antibody known as CD47 that blocks that signal.
In tests in mice, the team showed that the hydrogel can successfully generate chimeric antigen receptor (CAR) macrophages that specifically target glioma stem cells. And sure enough, the brain cancer didn’t return during the six-month period that the mice were monitored following the surgery.
While the hydrogel still needs to be tested in larger animals before it might ever find use in humans, the team says that the research is promising. It could be adapted to help treat other aggressive solid tumors as well, such as breast cancer, and together with another recent hydrogel the team developed to prevent cancer relapse, we might soon have a few new weapons in the arsenal.
“We have a lot of work to do before it can be potentially translated into the clinic, but we feel confident that this is a very promising approach for bringing new hope to patients with glioblastoma so they can recover after surgery,” said Hu. “We hope we can do our work to be able to advance this technology to the clinic.”
The research was published in the journal Science Translational Medicine.
Source: University of Wisconsin-Madison
