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A Self-Cascading Catalytic Therapy and Antigen Capture Scaffold-Mediated T Cells Augments for Postoperative Brain Immunotherapy
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A Self-Cascading Catalytic Therapy and Antigen Capture Scaffold-Mediated T Cells Augments for Postoperative Brain Immunotherapy

Bhanu Nirosha Yalamandala, Thrinayan Moorthy, Zhuo-Hao Liu, Thi My Hue Huynh, Hoi Man Iao, Wan-Chi Pan, Kang-Li Wang, Chi-Shiun Chiang, Wen-Hsuan Chiang, Lun-De Liao, …
Small (Weinheim an der Bergstrasse, Germany), 卷.21(5), 頁碼.e2406178-n/a
01/02/2025
PMID: 39676476
Web of Science ID: WOS:001377466000001

摘要

Animals Brain Neoplasms - immunology Brain Neoplasms - therapy Catalysis Cell Line, Tumor Glioblastoma - immunology Glioblastoma - therapy Humans Immunotherapy - methods Metal-Organic Frameworks - chemistry Mice T-Lymphocytes - immunology Brain
The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, the phenomenon of immune privilege and the generally low immunogenicity of vaccines often reduce the presence of lymphocytes within brain tumors, especially in brain tumor recurrence clusters. In this study, an implantable self-cascading catalytic therapy and antigen capture scaffold (CAS) that can boost catalytic therapy efficiency at post-surgery brain tumor and capture the antigens via urethane-polyethylene glycol-polypropylene glycol (PU-EO-PO) segments are developed for postoperative brain immunotherapy. The CAS consists of 3D-printed elastomers modified with iron (Fe ) metal-organic frameworks (MOFs, MIL88) and acts as a programmed peroxide mimic in cancer cells to initiate the Fenton reaction and sustain ROS production. With the assistance of chloroquine (CQ), autophagy is inhibited through lysosome deacidification, which interrupts the self-defense mechanism, further enhances cytotoxicity, and releases antigens. Then, CAS containing PU-EO-PO groups acts as an antigen depot to detain autologous tumor-associated antigens to dendritic cells maturation and T cell augments for sustained immune stimulation. CAS enhanced the immune response to postoperative brain tumors and improved survival through brain immunotherapy.

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2024 Small BN NY PU9.23 MB下載檢視
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url
https://doi.org/10.1002/smll.202406178檢視
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https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202406178檢視

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