Sunday, December 10, 2023

A gel that stops brain tumors in mice could be a hope for humans

A drug administered through a novel gel cured 100% of mice with aggressive brain cancer, a surprising result that offers new hope to patients diagnosed with glioblastoma, one of the deadliest and most common brain tumors in humans, as published in the journal magazine Proceedings of the National Academy of Sciences.

“Despite recent technological advances, there is a pressing need for new treatment strategies,” says Honggang Cui, a chemical and biomolecular engineer at Johns Hopkins University (United States) 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 grooves left after surgical removal of a brain tumor.

Areas that surgery does not reach

The gel can reach areas that surgery cannot reach and current drugs have difficulty reaching to kill persistent cancer cells and suppress tumor growth. It also seems to trigger an immune response that the mouse’s body has a hard time firing on its own in the fight against glioblastoma.

When the researchers re-attacked the surviving mice with a new glioblastoma tumor, their immune systems defeated the cancer on their own without additional medication. According to the researchers, the gel not only repels cancer, but also helps rewire the immune system to prevent its recurrence through immunological memory.

Still, surgery is essential to this approach, the researchers noted. Application of the gel directly to the brain without surgical removal of the tumor resulted in a 50% survival rate. “Surgery will likely relieve some of that pressure and allow more time for the gel to activate the immune system to fight cancer cells,” Cui explains.

Nano-sized filaments

The gel solution consists of nanometer-sized filaments made from paclitaxel, a drug approved for breast, lung and other types of cancer. The filaments serve as a vehicle to deliver an antibody called aCD47. By uniformly covering the tumor cavity, the gel consistently releases the medication for several weeks and its active ingredients remain close to the injection site.

By using that specific antibody, the team is attempting to overcome one of the most difficult hurdles in glioblastoma research. It targets macrophages, a type of cell that sometimes supports immunity but other times protects cancer cells, allowing aggressive tumor growth.

One of the gold standard therapies for glioblastoma is a wafer co-developed by a team of researchers at Johns Hopkins and the Massachusetts Institute of Technology in the 1990s, known commercially as gliadel. It is an FDA-approved biodegradable polymer that also delivers medication to the brain after surgical removal of the tumor.

The most impressive results

gliadel showed significant survival rates in laboratory experiments, but the results obtained with the new gel are among the most impressive the Johns Hopkins team has seen, according to Betty Tyler, co-author and associate professor of neurosurgery at Johns Hopkins School of Medicine. who played a pivotal role in the development of Gliadel.

“We don’t often see 100% survival in mouse models of this disease,” Tyler acknowledges. “To think that there’s a chance that this new combination of hydrogels could change that survival curve for glioblastoma patients is very exciting.”

The new gel offers hope for the future treatment of glioblastoma because it integrates anti-cancer drugs and antibodies, a combination of therapies that the researchers say is difficult to administer simultaneously due to the molecular composition of the ingredients. “This hydrogel combines intracranial chemotherapy and immunotherapy,” Tyler says. “The gel is implanted at the time of tumor resection, which makes it work really well.”

Henry Brem, study co-author at Johns Hopkins and co-developer of gliadel, in addition to other therapies against brain tumors currently in the clinical trial phase, emphasized the challenge of translating the results of the gel in the laboratory into therapies with substantial clinical repercussions. “The challenge we face now is to translate an exciting phenomenon from the laboratory to clinical trials,” says Brem, chief neurosurgeon at Johns Hopkins Hospital.

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