aCD47-docetaxel immuno-chemotherapy: A two-pronged attack against 'cold' glioblastoma.

Overcoming tumor heterogeneity, immunosuppression, and poor drug penetration remains a major challenge in treating glioblastoma (GBM). Here, we introduce a localized immuno-chemotherapy that combines the cytotoxic activity of docetaxel (DTXL) with the blockade of the 'do not eat me' signal via an anti-CD47 antibody (aCD47). Together, these agents act as a two-step immune-priming system, in which DTXL kills the tumor cells and exposes tumor antigens, while aCD47 amplifies this response by enabling macrophage-mediated clearance of the remaining tumor cells. To synchronize these mechanisms, both agents were co-delivered using μMESH, a pliable microstructured film placed directly over unresected tumors to enable precise, sustained local delivery. In syngeneic 'cold' GBM models, aCD47 or DTXL monotherapies modestly extended survival, whereas their combined delivery through μMESH reprogrammed the tumor microenvironment, enhanced T-cell recruitment, and generated a robust synergistic anti-tumor response. This treatment more than doubled median survival, with 40% of mice surviving beyond six months. These findings demonstrate that localized immuno-chemotherapy integrating DTXL and aCD47 can overcome immune resistance in unresected GBM, with μMESH serving as an effective platform for precise and sustained drug delivery.