APRIL 24, 2023
by Study Finds
BALTIMORE — A “miracle” gel that cures brain tumors in mice could offer new hope for human cancer patients, a new study reveals. Researchers at John Hopkins University say the medication delivered by the substance stops 100 percent of an aggressive form of brain cancer within mice. The “striking” result provides new hope for patients diagnosed with glioblastoma, one of the deadliest and most common brain tumors in humans.
“Despite recent technological advancements, there is a dire need for new treatment strategies. We believe this hydrogel will be the future and will supplement current treatments for brain cancer,” says Professor Honggang Cui of Johns Hopkins University.
Professor Cui’s team mixed an anti-cancer drug and an antibody in a solution that self-assembles into a gel to fill the tiny grooves left after a brain tumor is surgically removed. Study authors add that the gel can reach areas that surgery might miss, and current drugs struggle to access, in order to kill lingering cancer cells and suppress tumor growth.
Prof. Cui notes the gel also appears to trigger an immune response that a mouse’s body struggles to activate on its own when fighting glioblastoma. When researchers rechallenged surviving mice with a new glioblastoma tumor, their immune systems alone defeated the cancer without additional medication.
Prof. Cui adds that the gel seems to not only fend off cancer but also helps rewire the immune system to discourage recurrence with immunological memory. However, surgery is essential for the approach to work, as applying the gel directly in the brain without surgical removal of the tumor resulted in only a 50-percent survival rate.
“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,” Professor Cui says in a media release.
Scientists show how the liquid substance self-assembles into a gel when injected into a saline solution. CREDIT: Johns Hopkins University
Why is this gel so effective?
The gel solution consists of nano-sized filaments made with paclitaxel, an approved drug for breast, lung, and other cancers. The filaments provide a vehicle to deliver an antibody called aCD47. By blanketing the tumor cavity evenly, the gel releases medication steadily over several weeks, and its active ingredients remain close to the site of injection.
By using this specific antibody, the team aims to overcome one of the toughest 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 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, commercially known as Gliadel. It is a biodegradable polymer that also delivers medication into the brain after surgical tumor removal.
Study co-author Professor Betty Tyler says Gliadel showed significant survival rates in lab experiments, but the results achieved with the new gel are some of the most impressive the research team has seen.
“We don’t usually see 100% survival in mouse models of this disease. Thinking that there is potential for this new hydrogel combination to change that survival curve for glioblastoma patients is very exciting,” Prof. Tyler says.
“This hydrogel combines both chemotherapy and immunotherapy intracranially. The gel is implanted at the time of tumor resection, which makes it work really well.”
Johns Hopkins co-author Professor Henry Brem, who co-developed Gliadel and other brain tumor therapies currently in clinical trials, emphasizes the challenge of translating the gel’s lab results into therapies with substantial clinical impacts.
“The challenge for us now is to transfer this exciting laboratory phenomenon to clinical trials.”
Why is glioblastoma so deadly?
Glioblastoma is a highly aggressive and deadly form of brain cancer, primarily due to a combination of factors that make it difficult to treat effectively. Some of these factors include:
- Rapid growth: Glioblastoma cells divide and multiply quickly, leading to rapid tumor growth. This aggressive growth often results in increased pressure within the brain, causing neurological symptoms and complications.
- Infiltrative nature: Glioblastoma tumors infiltrate the surrounding brain tissue, making it challenging to surgically remove the entire tumor. Even when the majority of the tumor is removed, microscopic cancer cells may remain in the surrounding tissue, leading to recurrence.
- Blood-brain barrier: The blood-brain barrier is a protective layer that prevents many substances, including certain chemotherapy drugs, from entering the brain. This makes it difficult to deliver effective drug treatments to the tumor site.
- Heterogeneity: Glioblastoma tumors are highly heterogeneous, meaning they are composed of various cell types with different genetic mutations. This diversity makes it difficult to target the tumor with a single treatment approach.
- Resistance to treatment: Glioblastoma cells often develop resistance to radiation and chemotherapy, limiting the effectiveness of these treatments.
- Location: Glioblastomas typically arise in the cerebral hemispheres of the brain, which are responsible for critical functions such as movement, sensation, and cognition. This makes surgical intervention more risky, as damage to healthy brain tissue can result in severe neurological deficits.
These factors contribute to the high mortality rate associated with glioblastoma, with the average survival time being approximately 12 to 18 months following diagnosis. Despite ongoing research and advances in treatment, glioblastoma remains one of the most challenging cancers to treat effectively.
The new findings are published in the Proceedings of the National Academy of Sciences.
South West News Service writer Stephen Beech contributed to this report.
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