A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity.
A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity.
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DOI：
10.3389/fimmu.2018.00857
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发表时间：
2018
影响因子：
7.3
通讯作者：
Rossi AE
中科院分区：
文献类型：
--
作者：
Sherman H;Gitschier HJ;Rossi AE
肿瘤学研究的最新进展集中在自体免疫细胞治疗上。然而，这种类型的免疫疗法对癌症补救的有效性并不等同于所有患者或癌症类型。这表明需要更好的临床前筛选模型，更密切地概括体内肿瘤生物学。已建立的研究免疫疗法的杀肿瘤活性的方法是在标准组织培养容器中研究永生化癌细胞系或原代肿瘤细胞的二维（2D）单层培养物。事实上，检查免疫细胞迁移和侵袭的经证实的手段是透化支持物或Boyden室中的2D趋化性测定。尽管如此，更像体内三维（3D）的多细胞肿瘤球体正在迅速成为检查免疫细胞侵袭和肿瘤细胞毒性的首选模型。因此，我们通过结合96孔可渗透支持系统和96孔低附着微孔板开发了3D免疫肿瘤学模型。使用可渗透支持系统可以评估免疫细胞迁移，在本研究中，将其作为自然杀伤NK-92 MI细胞对人基质细胞衍生因子-1（SDF-1α）的趋化反应进行检测。通过测量NK-92 MI向在低附着微板中形成的肺癌A549细胞球体中的浸润来评估免疫侵袭。新配对的可渗透支持系统与低附着微孔板允许同时调查免疫细胞归巢，免疫肿瘤球体的入侵，和球体的细胞毒性。实际上，该系统代表了一种更全面的体内免疫肿瘤学模型，可用于高通量研究杀肿瘤活性。
The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate in vivo tumor biology. The established method for investigating tumoricidal activity of immunotherapies has been study of two-dimensional (2D) monolayer cultures of immortalized cancer cell lines or primary tumor cells in standard tissue culture vessels. Indeed, a proven means to examine immune cell migration and invasion are 2D chemotaxis assays in permeabilized supports or Boyden chambers. Nevertheless, the more in vivo-like three-dimensional (3D) multicellular tumor spheroids are quickly becoming the favored model to examine immune cell invasion and tumor cell cytotoxicity. Accordingly, we have developed a 3D immune oncology model by combining 96-well permeable support systems and 96-well low-attachment microplates. The use of the permeable support system enables assessment of immune cell migration, which was tested in this study as chemotactic response of natural killer NK-92MI cells to human stromal-cell derived factor-1 (SDF-1α). Immune invasion was assessed by measuring NK-92MI infiltration into lung carcinoma A549 cell spheroids that were formed in low-attachment microplates. The novel pairing of the permeable support system with low-attachment microplates permitted simultaneous investigation of immune cell homing, immune invasion of tumor spheroids, and spheroid cytotoxicity. In effect, the system represents a more comprehensive and in vivo-like immune oncology model that can be utilized for high-throughput study of tumoricidal activity.
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一种新型的三维异型球体模型，用于评估癌症免疫疗法的活性。
DOI：
10.1007/s00262-016-1927-1
发表时间：
2017-01
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Herter S;Morra L;Schlenker R;Sulcova J;Fahrni L;Waldhauer I;Lehmann S;Reisländer T;Agarkova I;Kelm JM;Klein C;Umana P;Bacac M
通讯作者：
Bacac M
影响因子：
4
作者：
Protti MP;De Monte L
通讯作者：
De Monte L
DOI：
10.1016/j.jconrel.2012.04.045
发表时间：
2012-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Mehta G;Hsiao AY;Ingram M;Luker GD;Takayama S
通讯作者：
Takayama S
影响因子：
--
作者：
Yu DS;Weng TH;Wu XX;Wang FXC;Lu XY;Wu HB;Wu NP;Li LJ;Yao HP
通讯作者：
Yao HP
影响因子：
3.7
作者：
Ekert, Jason E.;Johnson, Kjell;Colter, David C.
通讯作者：
Colter, David C.