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
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

e2310078

Subventions

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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Auteurs

Chunyan Zhu (C)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Lingjie Ke (L)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Xiang Ao (X)

Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, and Department of Orthopedics, 953 Hospital of PLA Army, Shigatse Branch of Xinqiao Hospital, Army Medical University, Chongqing, 400042, China.

Ying Chen (Y)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Hongwei Cheng (H)

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.

Huhu Xin (H)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China.

Xiang Xu (X)

Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, and Department of Orthopedics, 953 Hospital of PLA Army, Shigatse Branch of Xinqiao Hospital, Army Medical University, Chongqing, 400042, China.

Xian-Jun Loh (XJ)

Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore, 138634, Republic of Singapore.

Zibiao Li (Z)

Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore, 138634, Republic of Singapore.
Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road, Jurong Island, Singapore, 627833, Republic of Singapore.

Haiyan Lyu (H)

Department of Pharmacy, Xiamen Xianyue Hospital, Xiamen, 361012, China.

Qi Wang (Q)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Dandan Zhang (D)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Yuan Ping (Y)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China.

Caisheng Wu (C)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Yun-Long Wu (YL)

Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.

Classifications MeSH