Glioblastoma is an aggressive brain cancer that almost always recurs after surgery and radiochemotherapy. Now, researchers have developed a biodegradable implant that can be placed directly into the brain cavity after tumor removal. This so-called wafer, nicknamed CANDI, slowly releases drugs to myeloid cells—a certain immune cell population abundant in glioblastoma—”waking up” these immune cells and helping them fight off any leftover cancer cells.
In mice, this approach prevented tumor recurrence in over half of the cases, and also showed promising results in human tumor samples in the lab.
The paper, “Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence,” is published in Nature Biomedical Engineering and was authored by Yannik Kaiser, MD-candidate, and Ralph Weissleder, MD, Ph.D., of the Center for Systems Biology at Massachusetts General Hospital and Harvard Medical School.
The researchers investigated myeloid cells. They make up a large fraction of the tumor microenvironment, are typically immunosuppressive, and help cancer cells grow more freely.
The team asked whether it is possible to prevent glioblastoma from coming back after surgery by reprogramming these immune cells, through targeted delivery of drugs to specific sites in the brain. They wanted to see if this could help transform the tumor microenvironment to fight cancer, rather than support it.
To answer their question, the team designed a biodegradable wafer made from a crosslinked sugar-based material (cyclodextrin) that can slowly deliver a combination of immune-modulating drugs to myeloid cells. They first tested the material in vitro and then implanted these wafers into the surgical cavities of mice after glioblastoma removal and studied the effects with imaging, immune profiling and survival analyses. They also tested the wafer on freshly removed human glioblastoma tissue in the lab.
Once the wafer was taken up by immune cells called tumor-associated macrophages, it effectively reprogrammed the cells to produce interleukin-12, a powerful immune-stimulating molecule. This triggered the recruitment of cancer-killing T cells to the tumor site.
As a result, more than 50% of mice treated with the wafer remained tumor-free long term. Importantly, the researchers saw similar immune activation in human glioblastoma tissue, suggesting that the approach could work in patients.
While immunotherapy has revolutionized cancer treatment across many disease types, there is still not an FDA-approved immunotherapy treatment for glioblastoma.
This work provides proof-of-concept for a new immunotherapy, administered during surgery, that could reduce glioblastoma recurrence by engaging the body’s own immune system. It could complement existing treatments like chemotherapy and radiation, as well as other potential immunotherapeutic treatments in development, to give patients better long-term outcomes.
The research team is now working on refining the wafer design for human use, ensuring controlled drug release over longer periods and preparing for eventual clinical testing. The ultimate goal is to bring this approach into the operating room to benefit patients with glioblastoma.
More information:
Yannik Kaiser et al, Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence, Nature Biomedical Engineering (2025). DOI: 10.1038/s41551-025-01533-2
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