Injectable Hydrogel Targets Macrophages and Stops the Relapse of Glioblastoma

Glioblastoma (GBM) is a common and aggressive form of brain cancer that often recurs after surgery, but a research team at the University of Wisconsin-Madison (UWM) developed a hydrogel that can significantly boost immunity during the post-operative treatment, which the team hopes will improve the recovery rate of glioblastoma patients in the future.

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Engineering Macrophages to Target CD133 Glycoprotein

Glioblastoma is extremely aggressive due to the fact that the tumor cells infiltrate the surrounding tissues. Because the disease occurs in the brain, it is impossible for surgeons to remove as much tissue as possible in order to separate the tumor from the normal tissue, which results in a high recurrence rate in glioblastoma patients and greatly impairs long-term survival after treatment. 

Tracing and eradicating residual glioma stem cells (GSCs) after surgery is critical to preventing post-operative recurrence, but effective strategies remained elusive to researchers. In the latest study published in Science Translational Medicine, the UWM research team developed a hydrogel that can be injected into the brain cavity after tumor removal to slowly release drugs into the surrounding tissues to promote an anti-cancer immune response. 

Immune cells normally help the body fight against infectious invaders, but in the tumor environment, they may change into a form that suppresses the immune system and promotes cancer growth. As surgery triggers an influx of inflammatory macrophages into the surgical site, macrophages that were previously allies may instead contribute to cancer recurrence.

To take advantage of these macrophages and “turn them from enemy to ally,” the nanoparticles contained in UWM’s hydrogel reprogrammed macrophages to target a glycoprotein called CD133, one of the markers of cancer stem cells. The researchers also added an antibody, CD47, to enable macrophages to ignore signals from cancer cells to escape and to help trace and identify cancer cells and eliminate them. Preclinical results in mouse models also showed that the injectable hydrogel treatment successfully produced specific chimeric antigen receptor (CAR) macrophages targeting glioblastoma.

Drug Delivery with Hydrogel Reduces Relapse Rate of Glioblastoma After Surgery

Although the technique requires more work before entering the clinic, Quanyin Hu, one of the study’s authors and Assistant Professor at UWM School of Pharmacy, believes that the research demonstrates the promise of eradicating glioma stem cells and ultimately preventing glioblastoma relapse. It is a highly promising approach that can bring new hope to glioblastoma patients.

Despite the initial focus on glioblastoma, the team believes this approach will broadly apply to highly aggressive solid tumors, such as breast cancer, as the approach utilizes macrophages in the post-operative regions.

The next step for the team is to test the efficacy of hydrogel in larger animal models while continuing to monitor long-term efficacy and toxicity over a 4-6 month period. If proven effective in humans, hydrogel therapy may eliminate the need for post-operative chemotherapy or radiation therapy, reducing toxic side effects and improving patient prognosis.

Author

Richard Chau