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用于改善免疫疗法的相变聚合物疫苗

phase transitional polymeric vaccines for improved immunotherapy.

作者信息

Wang Jie, Wang Yi, Qiao Shenglin, Mamuti Muhetaerjiang, An Hongwei, Wang Hao

机构信息

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China.

出版信息

Natl Sci Rev. 2021 Aug 27;9(2):nwab159. doi: 10.1093/nsr/nwab159. eCollection 2022 Feb.

Abstract

Cancer vaccines have exhibited immense potential in cancer treatment. Through activating the host's immune system, vaccines stimulate extensive functional T cells to eliminate cancer. However, the therapeutic efficacy of cancer vaccines is limited by their inferior lymph node delivery and inadequate uptake of dendritic cells. Herein, we propose an phase transitional strategy on vaccine manufacturing to maximally enhance lymph node drainage while ensuring adequate dendritic cell uptake. The phase transitional vaccines, with dynamic size modulation property, retain a small size (24.4 ± 3.1 nm) during lymph node draining then transform into larger particles (483.0 ± 41.6 nm) on-site by external signal input. Results show that this strategy induced rapid and robust immune response in a mouse melanoma tumor model. Furthermore, a stronger humoral immune response was observed in mice when immunized with MHC-II restricted antigen, which demonstrated that lymph node-targeted cancer vaccine delivery could be effectively manipulated through dynamic size modulation.

摘要

癌症疫苗在癌症治疗中已展现出巨大潜力。通过激活宿主免疫系统,疫苗刺激大量功能性T细胞来消除癌症。然而,癌症疫苗的治疗效果受到其较差的淋巴结递送能力和树突状细胞摄取不足的限制。在此,我们提出一种疫苗制造的相变策略,以在确保树突状细胞充分摄取的同时,最大程度地增强淋巴结引流。这种相变疫苗具有动态尺寸调节特性,在淋巴结引流过程中保持较小尺寸(24.4±3.1纳米),然后通过外部信号输入在局部转变为较大颗粒(483.0±41.6纳米)。结果表明,该策略在小鼠黑色素瘤肿瘤模型中诱导了快速且强烈的免疫反应。此外,在用MHC-II限制性抗原免疫小鼠时,观察到更强的体液免疫反应,这表明通过动态尺寸调节可以有效操控靶向淋巴结的癌症疫苗递送。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/851a/8824734/1b63e93a49a0/nwab159fig1.jpg

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