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A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody

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机构: [1]Laboratory of Stem Cell Biology, Department of Radiology, Huaxi MR Research Centner (HMRRC), Department of Biotherapy, Cancer Center, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Functional and Molecular Imaging Key Laboratory of Sichuan Province, And Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China. [3]Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA.
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关键词: Cell membrane Biomimetic nanosystem Immunogenic cell death Immunotherapy anti-PD-L1 antibody

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To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as "eat me" signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.© 2022 The Authors.

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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第一作者机构: [1]Laboratory of Stem Cell Biology, Department of Radiology, Huaxi MR Research Centner (HMRRC), Department of Biotherapy, Cancer Center, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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