Yannik Kaiser, MD-candidate, and Ralph Weissleder, MD, PhD , of the Center for Systems Biology at Massachusetts General Hospital and Harvard Medical School are the lead and corresponding authors of a paper published in Nature Biomedical Engineering, " Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence ."
Q: How would you summarize your study for a lay audience?
Glioblastoma is an aggressive brain cancer that almost always recurs after surgery and radiochemotherapy. We 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.
Q: What question were you investigating?
Myeloid cells, which make up a large fraction of the tumor microenvironment, are typically immunosuppressive, helping cancer cells grow more freely. We 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. We wanted to see if this could help transform the tumor microenvironment to fight cancer, rather than support it.
Q: What methods or approach did you use?
We 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. We 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. We also tested the wafer on freshly removed human glioblastoma tissue in the lab.
Q: What did you find?
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, we saw similar immune activation in human glioblastoma tissue, suggesting that the approach could work in patients.
Q: What are the implications?
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.
Q: What are the next steps?
We are 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.
Authorship: In addition to Kaiser and Weissleder, Mass General Brigham authors include Christopher S. Garris, Hyung Shik Kim, Juhyun Oh, Elias A. Halabi, Moonhyun Choi, Sepideh Parvanian, and Rainer Kohler.
Paper cited: Kaiser, Y., et al. "Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence." Nature Biomedical Engineering. DOI: 10.1038/s41551-025-01533-2.
Funding: This work was partly supported by NIH grants (R01CA281735) and (R33CA277820), the Swiss Institute for Experimental Cancer Research and the German Academic Exchange Service.
Disclosures: R.W. is a consultant for Boston Scientific, Earli and Accure Health, none of whom contributed to or were involved in this research. R.W. is an inventor on multiple patents, all managed institutionally through Massachusetts General Brigham. D.M. is a consultant for Limula and MPC Therapeutics, scientific co-founder of Cellula Therapeutics and is an inventor on patents related to CAR–T cell therapy filed by the University of Pennsylvania, Istituto Oncologico della Svizzera Italiana (IOSI) and the University of Geneva. The remaining authors declare no competing interests.
