Recruiting T Cells towards Brain for Enhanced Glioblastoma Immunotherapeutic Efficacy by Co-delivery of Cytokines and Immune Checkpoint Antibodies with Macrophage Membrane-Camouflaged Nano Vesicles.

Immunotherapy with immune checkpoint inhibitors (CPIs) shows promising prospects for glioblastoma multiforme (GBM) while with restricted results, mainly attributed to the immunosuppressive tumor microenvironment (TME) and the limited antibody permeability of blood-tumor-barrier (BTB) in GBM. Here, we described a macrophage-mimicking membrane vesicle that co-delivering 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, tumor tropism of macrophage membrane and receptor mediated transcytosis of angiopeptide-2 peptide allowed the nano vesicle to effectively cross the BTB and target GBM region, with 19.75-fold higher antibodies accumulation compared to free aPD-L1 group. The CPI therapeutic efficacy was 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 the orthotopic GBM mice. The nano vesicle that relieving tumor immunosuppressive microenvironment by CXCL10 to enhance aPD-L1 efficacy might present a promising strategy for brain-tumor immunotherapy. This article is protected by copyright. All rights reserved.