A new hydrogel developed by researchers at Johns Hopkins University has cured 100% of mice with aggressive brain cancer by combining cancer drugs and antibodies to target lingering cancer cells and trigger an immune response against glioblastoma.
Drugs delivered by new gel cured 100% of mice with aggressive brain cancer, a striking finding that offers new hope to patients diagnosed with glioblastoma, one of the deadliest and most common brain tumors in man.
“Despite recent advances in technology, there is an urgent need for new treatment strategies,” said Honggang Cui, a chemical and biomolecular engineer from Johns Hopkins University who led the research. “We believe this hydrogel will be the future and complement current treatments for brain cancer.”
Cui’s team combined an anti-cancer drug and an antibody in a solution that self-assembles into a gel to fill in the tiny furrows left after surgical removal of a brain tumor. The gel can reach areas that surgery might miss and that current drugs struggle to reach to kill lingering cancer cells and suppress tumor growth. The results are published today in Proceedings of the National Academy of Sciences.
The gel also appears to trigger an immune response that a mouse’s body struggles to activate on its own when fighting glioblastoma. When the researchers retested surviving mice with a new glioblastoma tumor, their immune systems single-handedly beat the cancer without additional medication. The gel appears to not only ward off cancer, but also help rewire the immune system to discourage recurrence along with immunological memory, the researchers said.
Still, surgery is essential for this approach, the researchers said. Applying the gel directly to the brain without surgical removal of the tumor resulted in a 50% survival rate.
“Surgery probably relieves some of that pressure and gives the gel more time to activate the immune system to fight cancer cells,” Cui said.
A video clip shows how the liquid substance self-assembles into a gel when injected into a saline solution. Credit: Johns Hopkins University
The gel solution consists of nano-sized filaments made with paclitaxel, an FDA-approved drug for breast, lung, and other cancers. The filaments provide a vehicle to deliver an antibody called aCD47. By evenly covering the tumor cavity, the gel releases the drug steadily for several weeks and its active ingredients remain close to the injection site.
By using this specific antibody, the team is trying to overcome one of the most difficult hurdles in glioblastoma research. It targets macrophages, a type of cell that sometimes supports immunity but sometimes protects cancer cells, allowing aggressive tumor growth.
One of the go-to therapies for glioblastoma is a platelet co-developed by a team of researchers from Johns Hopkins and the Massachusetts Institute of Technology in the 1990s, commercially known as Gliadel. It is an FDA-approved biodegradable polymer that also delivers drugs to the brain after surgical removal of the tumor.
Gliadel showed significant survival rates in lab experiments, but the results with the new gel are among the most impressive the Johns Hopkins team has seen, said Betty Tyler, co-author and associate professor of neurosurgery. at the Johns Hopkins School of Medicine. who played a central role in the development of Gliadel.
“We don’t typically see 100% survival in mouse models of this disease,” Tyler said. “To think that this new combination of hydrogels has the potential to alter the survival curve of glioblastoma patients is very exciting.”
The new gel offers hope for the future treatment of glioblastoma because it incorporates cancer drugs and antibodies, a combination of therapies that researchers say are difficult to administer simultaneously due to the molecular makeup of the ingredients.
“This hydrogel combines both chemotherapy and intracranial immunotherapy,” Tyler said. “The gel is implanted at the time of tumor resection, which makes it very effective.”
Johns Hopkins co-author Henry Brem, who co-developed Gliadel in addition to other brain tumor therapies currently in clinical trials, highlighted the challenge of translating results from the gel in the lab into therapies with substantial clinical impacts.
“The challenge for us now is to transfer an exciting phenomenon from the laboratory to clinical trials,” said Brem, who is chief neurosurgeon at Johns Hopkins Hospital.
Reference: “Self-Assembled Paclitaxel Stimulation of Tumor-Associated Macrophages for the Postoperative Treatment of Glioblastoma” by Feihu Wang, Qian Huang, Hao Su, Mingjiao Sun, Zeyu Wang, Ziqi Chen, Mengzhen Zheng, Rami W. Chakroun, Maya K Monroe, Daiqing Chen, Zongyuan Wang, Noah Gorelick, Riccardo Serra, Han Wang, Yun Guan, Jung Soo Suk, Betty Tyler, Henry Brem, Justin Hanes and Honggang Cui, April 25, 2023, Proceedings of the National Academy of Sciences.
Other Johns Hopkins authors are Feihu Wang, Qian Huang, Hao Su, Mingjiao Sun, Zeyu Wang, Ziqi Chen, Mengzhen Zheng, Rami W. Chakroun, Maya K. Monroe, Daiqing Chen, Zongyuan Wang, Noah Gorelick, Riccardo Serra, Han Wang, Yun Guan, Jung Soo Suk, and Justin Hanes.