Tumor cell-derived engineered exosome enhances effective immunotherapy for orthotopic glioblastoma and its recurrences

Li, S; Zhang, D; Wang, Y; Ismail, M; He, W; Zheng, M; Shi, B; Zou, Y

Tumor cell-derived engineered exosome enhances effective immunotherapy for orthotopic glioblastoma and its recurrences

Li, S Zhang, D Wang, Y Ismail, M He, W Zheng, M Shi, B

Zou, Y

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Nano Today, 2025, 63, pp. 102748
Issue Date:: 2025-08-01

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Field	Value	Language
dc.contributor.author	Li, S
dc.contributor.author	Zhang, D
dc.contributor.author	Wang, Y
dc.contributor.author	Ismail, M
dc.contributor.author	He, W
dc.contributor.author	Zheng, M
dc.contributor.author	Shi, B https://orcid.org/0000-0002-1043-3163
dc.contributor.author	Zou, Y
dc.date.accessioned	2025-10-15T03:50:27Z
dc.date.available	2025-10-15T03:50:27Z
dc.date.issued	2025-08-01
dc.identifier.citation	Nano Today, 2025, 63, pp. 102748
dc.identifier.issn	1748-0132
dc.identifier.issn	1878-044X
dc.identifier.uri	http://hdl.handle.net/10453/190406
dc.description.abstract	Glioblastoma multiforme (GBM) is considered as one of the most lethal malignancies in the central neuron system (CNS). Despite significant advances in immunotherapy approaches for multiple tumors, the highly immunosuppressive tumor microenvironment (TME) of GBM presents critical challenges. Inspired by tumor-derived exosomes, which carry a range of tumor-associated antigens and possess improved blood-brain barrier (BBB) transcytosis, we have developed CpG adjuvant-functionalized GBM tumor-derived exosomes (Exo-CpG) to inhibit GBM proliferation and elicit long-lasting protective immunity via potent stimulation of the body's innate immunity. Our exosomal nanoplatform efficiently activates the antigen-presenting dendritic cells (DCs) in lymph nodes, promoting their maturation, and generating a strong T cell response. In combination with the anti-programmed cell death ligand-1 antibody (aPD-L1), these exosomes effectively restrain the growth of GBM in orthotopic primary GL261 and phosphatase and tensin homologue (PTEN)-deficient immunosuppressive CT2A models in immune-competent mice, significantly prolonging survival by effectively suppressing GBM recurrence. This fully natural exosomal nanoplatform offers a promising strategy for targeting the immunosuppressive TME of orthotopic primary GBM and its recurrences.
dc.language	en
dc.publisher	Elsevier
dc.relation.ispartof	Nano Today
dc.relation.isbasedon	10.1016/j.nantod.2025.102748
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0903 Biomedical Engineering, 1007 Nanotechnology
dc.subject.classification	Nanoscience & Nanotechnology
dc.subject.classification	3206 Medical biotechnology
dc.subject.classification	4003 Biomedical engineering
dc.subject.classification	4018 Nanotechnology
dc.title	Tumor cell-derived engineered exosome enhances effective immunotherapy for orthotopic glioblastoma and its recurrences
dc.type	Journal Article
utslib.citation.volume	63
utslib.for	0903 Biomedical Engineering
utslib.for	1007 Nanotechnology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-10-15T03:50:17Z
pubs.publication-status	Published
pubs.volume	63

Abstract:

Glioblastoma multiforme (GBM) is considered as one of the most lethal malignancies in the central neuron system (CNS). Despite significant advances in immunotherapy approaches for multiple tumors, the highly immunosuppressive tumor microenvironment (TME) of GBM presents critical challenges. Inspired by tumor-derived exosomes, which carry a range of tumor-associated antigens and possess improved blood-brain barrier (BBB) transcytosis, we have developed CpG adjuvant-functionalized GBM tumor-derived exosomes (Exo-CpG) to inhibit GBM proliferation and elicit long-lasting protective immunity via potent stimulation of the body's innate immunity. Our exosomal nanoplatform efficiently activates the antigen-presenting dendritic cells (DCs) in lymph nodes, promoting their maturation, and generating a strong T cell response. In combination with the anti-programmed cell death ligand-1 antibody (aPD-L1), these exosomes effectively restrain the growth of GBM in orthotopic primary GL261 and phosphatase and tensin homologue (PTEN)-deficient immunosuppressive CT2A models in immune-competent mice, significantly prolonging survival by effectively suppressing GBM recurrence. This fully natural exosomal nanoplatform offers a promising strategy for targeting the immunosuppressive TME of orthotopic primary GBM and its recurrences.

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http://hdl.handle.net/10453/190406