Injectable Supramolecular Hydrogels for In Situ Programming of Car-T Cells toward Solid Tumor Immunotherapy.
CAR-T cells
immunotherapy
solid tumors
supramolecular hydrogel
sustained-release system
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
10 Nov 2023
10 Nov 2023
Historique:
revised:
06
11
2023
received:
28
09
2023
pubmed:
10
11
2023
medline:
10
11
2023
entrez:
10
11
2023
Statut:
aheadofprint
Résumé
Chimeric antigen receptor (CAR)-T cell immunotherapy is approved in the treatment of hematological malignancies, but remains far from satisfactory in solid tumor treatment due to inadequate intra-tumor CAR-T cell infiltration. Herein, an injectable supramolecular hydrogel system, based on self-assembly between cationic polymer mPEG-PCL-PEI (PPP) conjugated with T cell targeting anti-CD3e f(ab')2 fragment and α-cyclodextrin (α-CD), is designed to load plasmid CAR (pCAR) with a T cell specific CD2 promoter, which successfully achieves in situ fabrication and effective accumulation of CAR-T cells at the tumor site in humanized mice models. More importantly, due to this tumor microenvironment reprogramming, secretion of cellular inflammatory cytokines (interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)) or tumor killer protein granzyme B is significantly promoted, which reverses the immunosuppressive microenvironment and significantly enhances the intra-tumor CAR-T cells and cytotoxic T cells infiltration. To the best of the current knowledge, this is a pioneer report of using injectable supramolecular hydrogel for in situ reprogramming CAR-T cells, which might be beneficial for solid tumor CAR-T immunotherapy.
Identifiants
pubmed: 37947048
doi: 10.1002/adma.202310078
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2310078Subventions
Organisme : Natural Science Foundation of China
ID : 81971724
Organisme : Natural Science Foundation of China
ID : 82173750
Organisme : Natural Science Foundation of China
ID : 82372119
Organisme : National Key R&D Program of China
ID : 2020YFA0908100
Informations de copyright
© 2023 Wiley-VCH GmbH.
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