An Inter-Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer.
An Inter-Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer.
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基于自然杀伤细胞的用于癌症联合免疫疗法和病毒疗法的补充生物杂交系统
DOI：
10.1002/advs.202103470
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Ding L;Gao Q;Xu Z;Cai L;Chen S;Zhang X;Cao P;Chen G
溶瘤腺病毒（Oncolytic adenovirusAds，Ads）因其能直接引起溶瘤感染并间接诱导抗肿瘤免疫而在肿瘤治疗中受到广泛关注。然而，它们的功效受到宿主抗病毒免疫应答、不良肿瘤递送和免疫抑制性肿瘤微环境（TME）的影响。在这里，自然杀伤（NK）细胞介导的Ad递送系统（Ad@NK）是通过利用两种组分的优点来产生的，用于癌症的联合免疫治疗和病毒治疗。在这种生物杂交系统中，具有肿瘤归巢向性的NK细胞充当生物反应器和庇护所，用于加载、保护、复制、扩增和释放Ad，从而导致高效的全身肿瘤靶向递送。作为反馈，Ad感染通过以STAT 4-颗粒酶B-依赖性方式激活I型干扰素信号传导，为NK细胞提供增强的抗肿瘤免疫力。Ad@NK系统可通过促进树突状细胞的成熟和巨噬细胞向M1表型的极化来缓解TME中的免疫抑制。体外和体内实验数据均表明Ad@NKs通过破坏肿瘤细胞、诱导免疫原性细胞死亡和免疫调节TME而具有优异的抗肿瘤和抗转移功能。这项工作为基于互补生物杂交系统的改进溶瘤病毒疗法与NK细胞疗法的组合提供了临床基础。通过利用两种组分的优点开发基于自然杀伤细胞的溶瘤腺病毒递送系统，用于三阴性乳腺癌的联合免疫治疗和病毒治疗。该系统对肿瘤的发展和转移的强大治疗功效证明了这种组合策略的巨大转化潜力。
Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell‐mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor‐homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor‐targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4‐granzyme B‐dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter‐supplementary biohybrid system. A natural killer cell‐based oncolytic adenovirus delivery system is developed by harnessing the merits of the two components for combinational immunotherapy and virotherapy of triple‐negative breast cancer. The powerful therapeutic efficacy of this system against the development and metastasis of tumors demonstrates the great translational potential of this combinational strategy.
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DOI：
10.3904/kjim.2015.30.5.580
发表时间：
2015-09
期刊：
The Korean journal of internal medicine
影响因子：
--
作者：
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通讯作者：
Baik SK
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影响因子：
17.1
作者：
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通讯作者：
Zhang, Xian-Zheng
影响因子：
4.7
作者：
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通讯作者：
Pentimalli, Francesca
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影响因子：
17.1
作者：
Chen, Zhikuan;Liu, Lanlan;Cai, Lintao
通讯作者：
Cai, Lintao
影响因子：
10.3
作者：
Duebgen, Matthias;Martinez-Quintanilla, Jordi;Shah, Khalid
通讯作者：
Shah, Khalid