DataVXAdvanced MaterialsPaper
journal article·2024-02

Injectable Supramolecular Hydrogels for In Situ Programming of Car‐T Cells toward Solid Tumor Immunotherapy

Chunyan Zhu, Lingjie Ke, Xiang Ao, Ying Chen, Hongwei Cheng, Huhu Xin, Xiang Xu, Xian‐Jun Loh, Zibiao Li, Haiyan Lyu, Qi Wang, Dandan Zhang, Yuan Ping, Caisheng Wu, Yun‐Long Wu

Advanced Materials· Volume 36· Issue 5
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Source abstract

Abstract

Abstract 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.
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Research context

Polymers

OpenAlex topics: CAR-T cell therapy research · Nanowire Synthesis and Applications · Immunotherapy and Immune Responses

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

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

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

College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Liangzhu Laboratory Zhejiang University Medical Center Hangzhou 311121 China

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

Department of Pharmacy Xiamen Xianyue Hospital Xiamen 361012 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China

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