Macrophages as drug carriers for the treatment of glioblastoma

Glioblastoma is the most common and most aggressive primary brain tumor in adults. Patients have a poor prognosis, in large part because of inadequate drug delivery. In addition, glioma tumor cells are able to create a tumor-promoting microenvironment through recruitment of peripheral immune cells, particularly macrophages. Miaomiao Sun, Maciej Bialasek and Tobias Weiss leveraged this tumor mechanism to overcome the challenge of suboptimal drug delivery by developing a novel macrophage-based drug delivery strategy. 

From different mouse and human glioblastoma models, the prize winners engineered macrophages to carry a so-called ferritin-conjugated cytotoxic payload (MMAE), and evaluated their ability to transfer the drug into glioblastoma cells. Macrophages are large, mobile cells of the immune system that remove pathogens and damaged cells. A ferritin–drug conjugate is a way of packaging a drug by attaching it to ferritin, a protein that naturally occurs in the human body. In other words: The young scientists used macrophages and a carrier structure to deliver the anti-cancer drug directly to the specific tumor cells in the brain. 

The results are very promising: In preclinical glioblastoma models, macrophage-drug conjugate (MDC) therapy showed strong anti-tumor efficacy, prolonged survival, and favorable immune responses. In addition, the MDC therapy achieved a reprogramming of the immunosuppressive tumor microenvironment by activation of T-lymphocytes and B-lymphocytes and reduction of immunosuppressive regulatory T-cells. The cytotoxic effect was limited to tumors and thus demonstrated an excellent safety profile.

Sun M*, Bialasek M*, Weiss T et al. Adoptive cell therapy with macrophage-drug conjugates facilitates cytotoxic drug transfer and immune activation in glioblastoma models. Sci. Transl. Med. 2025; 17, eadr4058. DOI:10.1126/scitranslmed.adr4058.  
*Contributed equally