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通过纳米制造增强T细胞对肿瘤的反应。

Augmenting T-cell responses to tumors by nanomanufacturing.

作者信息

Hasani-Sadrabadi Mohammad Mahdi, Majedi Fatemeh S, Miller Matthew L, Thauland Timothy J, Bouchard Louis-S, Li Song, Butte Manish J

机构信息

Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA.

Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095 USA.

出版信息

Mater Horiz. 2020 Nov 1;7(11):3028-3033. doi: 10.1039/d0mh00755b. Epub 2020 Sep 29.

Abstract

Recent innovations in immunoregulatory treatments have demonstrated both the impressive potential and vital role of T cells in fighting cancer. These treatments come at a cost, with systemic side effects including life-threatening autoimmunity and immune dysregulation the norm. Here, we developed an approach to locally synthesize immune therapies and in this way, avoid systemic toxicity. Rather than just encapsulating cytokines, we endowed our nanoparticles with transcriptional and translational machinery to cytokines locally, , and on demand (activated by light). We demonstrated the capabilities of these particles and , in a mouse model of melanoma, and showed that tumor-infiltrating T cells were more highly activated in the context of these "microfactory" particles that make the synthetic cytokine.

摘要

免疫调节治疗领域的最新创新成果彰显了T细胞在对抗癌症方面令人瞩目的潜力和至关重要的作用。这些治疗方法存在一定代价,全身性副作用包括危及生命的自身免疫和免疫失调是常见现象。在此,我们开发了一种局部合成免疫疗法的方法,以此避免全身毒性。我们的纳米颗粒并非仅仅包裹细胞因子,而是配备了转录和翻译机制,能够根据需要(通过光激活)在局部合成细胞因子。我们在黑色素瘤小鼠模型中展示了这些颗粒的功能,并表明在这些能够合成细胞因子的“微型工厂”颗粒环境中,肿瘤浸润T细胞的激活程度更高。

相似文献

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Augmenting T-cell responses to tumors by nanomanufacturing.通过纳米制造增强T细胞对肿瘤的反应。
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本文引用的文献

1
Autoimmune complications of cancer immunotherapy.癌症免疫治疗的自身免疫并发症。
Curr Opin Immunol. 2019 Dec;61:54-59. doi: 10.1016/j.coi.2019.08.004. Epub 2019 Sep 23.
5
Synthetic Cells Synthesize Therapeutic Proteins inside Tumors.合成细胞在肿瘤内合成治疗性蛋白。
Adv Healthc Mater. 2018 May;7(9):e1701163. doi: 10.1002/adhm.201701163. Epub 2017 Dec 28.
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Cytokines in Cancer Immunotherapy.细胞因子在癌症免疫治疗中的作用
Cold Spring Harb Perspect Biol. 2018 Dec 3;10(12):a028472. doi: 10.1101/cshperspect.a028472.
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Role of IL-2 in cancer immunotherapy.白细胞介素-2在癌症免疫治疗中的作用。
Oncoimmunology. 2016 Apr 25;5(6):e1163462. doi: 10.1080/2162402X.2016.1163462. eCollection 2016 Jun.

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