Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy
Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy
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基于铁蛋白纳米粒子的 SpyTag/SpyCatcher 启用的点击疫苗用于肿瘤免疫治疗
DOI：
10.1016/j.nano.2018.11.009
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发表时间：
2019-02-01
影响因子：
5.4
通讯作者：
Zhu, Mingzhao
中科院分区：
文献类型：
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作者：
Wang, Wenjun;Liu, Zhida;Zhu, Mingzhao
近年来，肿瘤新抗原已成为开发个人治疗性疫苗的吸引力。然而，如何立即递送多种新抗原以获得有效的抗肿瘤免疫仍然具有挑战性。在这里，我们建立了SpyCatcher修饰的铁蛋白纳米颗粒平台，其允许以点击链接方式与含有SpyTag的肿瘤特异性抗原进行方便且稳定的共价缀合。这些铁蛋白纳米颗粒在皮下免疫后迅速引流至淋巴结并靶向树突状细胞，特别是CD 8 α（+）群体。携带HPV 16癌基因E7肽抗原或MC 38肿瘤衍生的突变体新抗原的铁蛋白纳米颗粒引起比可溶性肽抗原增强约2-3倍的抗原特异性细胞毒性T淋巴细胞（CTL）应答，并显著抑制E7相关或MC 38肿瘤的生长。与PD-1检查点阻断联合使用，抗肿瘤作用进一步增强。总之，我们的研究提供了一个基于铁蛋白纳米颗粒的SpyTag/SpyCatcher点击疫苗平台，特别是用于个性化的小免疫治疗。(C)2018爱思唯尔公司All rights reserved.
Recently, tumor neoantigens have been attractive for development of personal therapeutic vaccines. However, how to instantly deliver multiple neoantigens for efficient anti-tumor immunity is still challenging. Here, we established a SpyCatcher-modified ferritin nanoparticle platform, which permits convenient and stable covalent conjugation with tumor specific antigens containing SpyTag in a click-link manner These ferritin nanoparticles are rapidly drained to lymph nodes and target dendritic cells, especially CD8 alpha(+) population, upon subcutaneous immunization. Ferritin nanoparticles carrying HPV16 oncogene E7 peptide antigen or MC38 tumor derived mutant neoantigens elicit about 2-3 folds enhanced antigen-specific cytotoxic T lymphocyte (CTL) response than soluble peptide antigens and significantly suppress the growth of E7-related or MC38 tumors. The anti-tumor effect was further enhanced in combination with PD-1 checkpoint blockade. Together, our study provides a ferritin nanoparticle-based, SpyTag/SpyCatcher-enabled click vaccine platform, especially for personalized minor immunotherapy. (C) 2018 Elsevier Inc. All rights reserved.