A gel applied directly into the brain could offer new hope for patients diagnosed with glioblastoma, the most common malignant brain tumor in adults.
The gel cured 100% of lab mice with glioblastoma when it was applied to the tumor cavity following surgery to remove the cancer, said senior researcher Honggang Cui, an associate professor of chemical and biomolecular engineering with Johns Hopkins University in Baltimore.
The gel provides a workaround to some special challenges inherent in the treatment of brain cancer. The blood-brain barrier hampers the ability of cancer drugs to get into the brain, and immune response to brain tumors tends to be blunted, the researchers noted.
Surgical removal of tumors is the standard of care for glioblastoma, but “the surgeon cannot remove all the tumor cells,” Cui said. “Some are left behind, and the cancer may come back.”
The experimental gel fills in tiny grooves and irregular surfaces left in the brain after a tumor is removed, reaching areas that surgery might miss to kill lingering cancer cells.
Glioblastomas are the fastest-growing brain tumors, and they are nearly always advanced when detected. Five-year survival rates are 22% for people ages 20 to 44, 9% for adults ages 45 to 54 and 6% for those ages 55 to 64, according to the American Cancer Society.
The hydrogel is made of paclitaxel, a chemotherapy drug. This allows the chemo — which cannot get through the blood-brain barrier when administered by IV — to be “self-delivered” to the site of the brain tumor, Cui said.
The paclitaxel gel is then loaded up with an immunotherapy antibody called aCD47. This antibody removes the ability of tumors to hide from the immune system, allowing immune cells to target and destroy any stray cancer cells left behind.
By blanketing the tumor cavity evenly, the gel releases medication steadily into the cancer site over several weeks, researchers said.
“When you put an immunotherapy agent together with a chemo drug, they can work synergistically,” Cui explained. “The active mechanism is different from either chemotherapy or immunotherapy. It is a combination of both.”
The gel also seemed to trigger an immune response that protected mice against future brain cancers.
When researchers introduced a new glioblastoma tumor into the surviving mice, their immune systems beat the cancer on their own without any additional medicine.
However, surgery is still needed for this new approach, Cui said. When researchers applied the gel without removing the glioblastoma, only 50% of the mice survived.
“The surgery likely alleviates some of that pressure and allows more time for the gel to activate the immune system to fight the cancer cells,” Cui said.
The study was published April 25 in the Proceedings of the National Academy of Sciences.
The gel needs further testing in mice and primates before it will be ready to be tried in humans, Cui noted.
But Dr. David Reardon, clinical director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute in Boston, said that “this approach is very likely able to be transferred to human patients and offers great hope to improve outcomes associated with these devastating tumors.
“By applying it directly into the tumor resection cavity in the brain, the therapy overcomes one of the critical limiting factors for effective brain tumor therapy, which is the blood-brain barrier,” said Reardon, who was not involved in the research.
Reardon added that the gel’s activity could be further enhanced by adding in other immunotherapy or targeted therapy drugs, and through repeat applications.
“One challenge for optimal translation to human patients is that the agent may require repeat serial dosing over time. Current state-of-the-art neurosurgical capabilities, however, should be able to make repeated dosing safe and of greater benefit,” Reardon said.
The American Cancer Society has more about brain and spinal cord tumors.
SOURCES: Honggang Cui, PhD, associate professor, chemical and biomolecular engineering, Johns Hopkins University, Baltimore; David Reardon, MD, clinical director, Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston; Proceedings of the National Academy of Sciences, April 25, 2023
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