TRAIL Coated Genetically Engineered Immunotherapeutic Nano-Ghosts Vesicles Target Human Melanoma-Avoiding the Need for High Effective Therapeutic Concentration of TRAIL
TRAIL Coated Genetically Engineered Immunotherapeutic Nano-Ghosts Vesicles Target Human Melanoma-Avoiding the Need for High Effective Therapeutic Concentration of TRAIL
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TRAIL 涂层基因工程免疫治疗纳米鬼囊泡靶向人类黑色素瘤 - 避免了对 TRAIL 高效治疗浓度的需求
DOI：
10.1002/adfm.202105701
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发表时间：
2021
影响因子：
19
通讯作者：
Levy L
中科院分区：
文献类型：
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作者：
Levy L
使用细胞毒性T淋巴细胞（CTL）或间充质干细胞（MSC）的癌细胞治疗由于细胞对宿主诱导的变化的易感性而具有障碍。在这里，多功能的无生命的广泛适用的纳米囊泡，称为免疫球蛋白纳米鬼（iNG），配备了固有的表面相关的靶向和治疗能力，其中MSC治疗和T细胞免疫治疗的承诺和好处结合成一个强大的现成的方法来治疗恶性疾病。为了模拟T细胞的细胞毒性或免疫抑制功能，iNG由MSC产生，所述MSC被遗传工程化（GE）或代谢操纵以表达额外的膜结合蛋白，从而赋予由此衍生的NG额外的表面相关功能，例如肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）。来自GE-MSC的iNG（GE-iNG）在体外显示出上级的TRAIL保留并在不同的癌细胞系中诱导凋亡。对人黑色素瘤模型的体内研究表明，全身性、三天一次的GE-iNG给药产生的肿瘤抑制作用与高出六个数量级浓度的可溶性TRAIL相当。因此，iNG是一种有前途的纳米囊泡平台，可以以非免疫原性方式影响肿瘤，同时避免对高效治疗浓度的需求。
Cancer cell therapy using cytotoxic T lymphocytes (CTL) or mesenchymal stem cells (MSC) possesses hurdles due to the cells, susceptibility to host induced changes. Here, versatile inanimate broadly applicable nanovesicles, termed immunotherapeutic‐nano‐ghosts (iNGs), are armed with inherent surface‐associated targeting and therapeutic capabilities in which the promise and benefits of MSC therapy and T cell immunotherapy are combined into one powerful off‐the‐shelf approach for treating malignant diseases. To mimic the cytotoxic or immunosuppressive functions of T cells, iNG are produced from MSC that were genetically engineered (GE) or metabolically manipulated to express additional membrane‐bound proteins, endowing the NGs derived therefrom with additional surface‐associated functions such as tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL). iNGs from GE‐MSCs (GE‐iNGs) show superior TRAIL retention and induce apoptosis in different cancer cell lines in vitro. In vivo studies on a human melanoma model demonstrate that a systemic, three‐day frequency, administration of GE‐iNGs result in tumor inhibition comparable to a six orders of magnitude higher concentration of soluble TRAIL. The iNGs are therefore a promising nanovesicle platform that can affect tumors in a non‐immunogenic manner while avoiding the need for a highly effective therapeutic concentration.