Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis.
Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis.
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DOI：
10.3390/jof6040231
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发表时间：
2020-10-17
期刊：
影响因子：
--
通讯作者：
Chai LYA
中科院分区：
文献类型：
--
作者：
Soe WM;Lim JHJ;Williams DL;Goh JG;Tan Z;Sam QH;Chotirmall SH;Ali NABM;Lee SC;Seet JE;Ravikumar S;Chai LYA
侵袭性曲霉病(IA)是恶性血液病患者的主要机会性真菌感染。尽管进行了抗真菌治疗，但发病率和死亡率仍然很高，因为免疫系统的受损状态阻碍了宿主对传统治疗的最佳反应。这引发了将免疫疗法作为辅助治疗的考虑。在这项研究中，我们评估了体外和体内扩增的人NK细胞作为抗烟曲霉菌感染的有效性。用表达4-1BB配体的转基因K562细胞和膜结合型白介素15(K562-41BBL-mBIL-15)作为饲养物，扩增和激活NK细胞。在体外杀灭实验和体内过继细胞治疗实验中观察了这些细胞的有效性。扩增的NK细胞在低效靶比(2：1)下具有较强的杀伤活性。杀菌活性呈形态依赖，对烟曲霉分生孢子最有效。杀菌活性是通过扩增的NK细胞上的Dectin-1受体介导的，从而增加穿孔素的释放，从而增强直接细胞溶解。在免疫低下的小鼠肺曲霉菌病模型中，我们发现NK细胞治疗显著减少了真菌负荷，从而证明了扩增的NK细胞作为免疫低下患者治疗IA的辅助治疗的翻译潜力。
Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients.
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影响因子：
7.7
作者：
Chiba S;Ikushima H;Ueki H;Yanai H;Kimura Y;Hangai S;Nishio J;Negishi H;Tamura T;Saijo S;Iwakura Y;Taniguchi T
通讯作者：
Taniguchi T
DOI：
10.1158/1078-0432.ccr-10-0735
发表时间：
2010-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cho D;Shook DR;Shimasaki N;Chang YH;Fujisaki H;Campana D
通讯作者：
Campana D
影响因子：
4.5
作者：
Klingemann, HG;Martinson, J
通讯作者：
Martinson, J
影响因子：
5.8
作者：
Chai, Louis Y. A.;Vonk, Alieke G.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
5.2
作者：
Pagano, Livio;Akova, Murat;Blijlevens, Nicole
通讯作者：
Blijlevens, Nicole