Recruiting T‐Cells toward the Brain for Enhanced Glioblastoma Immunotherapeutic Efficacy by Co‐Delivery of Cytokines and Immune Checkpoint Antibodies with Macrophage‐Membrane‐Camouflaged Nanovesicles

• DOI: 10.1002/adma.202209785
• Publication Date: 2023-04-27T03:04:21Z
• Authors: Xiaoxuan Xu; Zhiqi Zhang; Jiawei Du; Yonger Xue; Xin Chen; Jianqiong Zhang; Xue Yang; Di Chang; Jinbing Xie; Shenghong Ju
• Keywords: Immune checkpoint

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