Immunotherapy with
immune checkpoint inhibitors (CPIs) shows promising prospects for
glioblastoma multiforme (GBM) but with restricted results, mainly attributed to the immunosuppressive tumor microenvironment (TME) and the limited antibody permeability of the blood-
tumor barrier (BTB) in GBM. Here, nanovesicles with a macrophage-mimicking membrane are described, that co-deliver chemotactic
CXC chemokine ligand 10 (CXCL10), to pre-activate the immune microenvironment, and anti-
programmed death ligand 1 antibody (aPD-L1), to interrupt the immune checkpoint, aiming to enhance the effect of GBM
immunotherapy. Consequently, the
tumor tropism of the macrophage membrane and the receptor-mediated transcytosis of the
angiopep-2 peptide allow the nanovesicle to effectively cross the BTB and target the GBM region, with 19.75-fold higher accumulation of
antibodies compared to the free aPD-L1 group. The
CPI therapeutic efficacy is greatly enhanced by CXCL10-induced T-cells recruitment with significant expansion of CD8+ T-cells and effector memory T-cells, leading to the elimination of
tumor, prolonged survival time, and long-term immune memory in orthotopic GBM mice. The nanovesicles, that relieve the
tumor immunosuppressive microenvironment by CXCL10 to enhance aPD-L1 efficacy, may present a promising strategy for
brain-tumor immunotherapy.