Self-Assembling Paclitaxel-Mediated Stimulation of Tumor-Associated Macrophages for Postoperative Treatment of Glioblastoma
By Feihu Wang, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, April 25, 2023
A medication delivered via a novel gel cured 100% of mice with an aggressive brain cancer.
This striking result offers new hope for patients diagnosed with glioblastoma, one of the deadliest and most common brain tumors in humans.
As recently highlighted in the Proceedings of the National Academy of Sciences, a research team at Johns Hopkins combined an anticancer 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.
The gel can reach areas that surgery might miss and current drugs struggle to reach to kill lingering cancer cells and suppress tumor growth.
The results were published recently.
The gel also seems to trigger an immune response that a mouse¡¯s body struggles to activate on its own when fighting glioblastoma.
When the researchers introduced a new glioblastoma tumor into surviving mice, their immune systems alone beat the cancer without additional medication.
Why? The gel appears not only to fend off cancer but to help rewire the immune system to discourage recurrence with immunological memory.
The researchers said, ¡°surgery is still essential for this approach.¡±
Applying the gel directly in the brain without surgical removal of the tumor resulted in only a 50% survival rate.
According to the researchers, ¡°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.¡±
The gel solution consists of nano-sized fil-aments made with paclitaxel, an FDA-approved drug for breast, lung, and other cancers.
The filaments also provide a vehicle to deliver an antibody called CD47.
By blanketing the tumor cavity evenly, the gel releases medication steadily over several weeks, and its active ingredients remain close to the injection site.
By using that specific antibody, the team is trying 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.
The new gel offers hope for future glioblastoma treatment because it integrates anticancer drugs and antibodies, a combination of therapies researchers say is difficult to administer simultaneously because of the molecular composition of the ingredients.
Another Johns Hopkins researcher said, ¡°The challenge now is to transfer an exciting laboratory phenomenon to clinical trials.¡±