Affiliation:
1. Jiangsu Key Laboratory of Molecular and Functional Imaging Department of Radiology Zhongda Hospital Medical School of Southeast University 87 DingJiaQiao Road Nanjing 210009 P. R. China
2. Center for BioDelivery Sciences School of Pharmacy Shanghai Jiao Tong University Shanghai 200240 China
3. Department of Microbiology and Immunology Medical School Southeast University Nanjing 210009 China
Abstract
AbstractImmunotherapy 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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
4 articles.
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