Interventional Optical Imaging-Monitored Synergistic Effect of Radio-Frequency Hyperthermia and Oncolytic Immunotherapy.
Interventional Optical Imaging-Monitored Synergistic Effect of Radio-Frequency Hyperthermia and Oncolytic Immunotherapy.
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DOI：
10.3389/fonc.2021.821838
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发表时间：
2021
影响因子：
4.7
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Zheng H;Zhang F;Monsky W;Ji H;Yang W;Yang X
发展一种基于吲哚菁绿色（ICG）的介入光学成像（OI）新技术，用于监测射频热疗（RFH）增强溶瘤免疫治疗的协同效应。本研究包括（1）优化VX 2肿瘤细胞内摄取ICG的剂量和检测时间窗;（2）体外验证使用基于ICG的OI评估RFH增强的溶瘤治疗（LTX-401）对VX 2细胞的疗效的能力;和（3）介入性OI监测的体内验证，使用具有原位肝VX 2肿瘤的兔模型的肿瘤内RFH增强的溶瘤免疫疗法。将体外和体内实验均分成具有不同处理的四个研究组（n=6/组）：（1）RFH+LTX-401的组合疗法;（2）在42 ℃下单独RFH 30分钟;（3）用LTX-401的溶瘤疗法;和（4）用盐水的对照。对于体内验证，使用新的多功能灌注-热射频消融电极治疗原位肝VX 2肿瘤，该电极能够在肿瘤内和肿瘤边缘同时递送LTX-401和RFH。在体外实验中，VX 2细胞对ICG的摄取从0 μg/mL线性增加到100 μg/mL，而ICG信号强度（SI）在24小时达到峰值。MTS检测和凋亡分析显示，联合治疗组细胞活力最低，凋亡率最高，与三种单药治疗组相比，差异有统计学意义（P<0.005）。在体内实验中，与其他单一疗法相比，超声成像检测到联合疗法的最小相对肿瘤体积（P<0.005）。在体外和体内实验中，基于ICG的介入光学成像检测到联合治疗的SI显著降低（P<0.005），这被“金标准”光学/X射线成像证实（P<0.05）。病理学和实验室检查进一步证实，与其他三个对照组相比，联合治疗组的Ki-67染色显示细胞增殖显著降低，TUNEL法显示细胞凋亡指数显著增加，免疫染色显示CD 8和CD 80阳性细胞数量显著增加（P<0.005）。我们提出了一种新的介入肿瘤学技术，介入光学成像监测的RFH增强溶瘤免疫治疗，这可能会开辟新的途径，有效地管理那些患者更大，不规则和不可切除的恶性肿瘤，不仅在肝脏，但也可能在其他器官。
To develop a new interventional oncology technique using indocyanine green (ICG)-based interventional optical imaging (OI) to monitor the synergistic effect of radiofrequency hyperthermia (RFH)-enhanced oncolytic immunotherapy. This study included (1) optimization of ICG dose and detection time-window for intracellular uptake by VX2 tumor cells; (2) in-vitro confirmation of capability of using ICG-based OI to assess efficacy of RFH-enhanced oncolytic therapy (LTX-401) for VX2 cells; and (3) in-vivo validation of the interventional OI-monitored, intratumoral RFH-enhanced oncolytic immunotherapy using rabbit models with orthotopic liver VX2 tumors. Both in-vitro and in-vivo experiments were divided into four study groups (n=6/group) with different treatments: (1) combination therapy of RFH+LTX-401; (2) RFH alone at 42°C for 30 min; (3) oncolytic therapy with LTX-401; and (4) control with saline. For in-vivo validation, orthotopic hepatic VX2 tumors were treated using a new multi-functional perfusion-thermal radiofrequency ablation electrode, which enabled simultaneous delivery of both LTX-401 and RFH within the tumor and at the tumor margins. In in-vitro experiments, taking up of ICG by VX2 cells was linearly increased from 0 μg/mL to 100 μg/mL, while ICG-signal intensity (SI) reached the peak at 24 hours. MTS assay and apoptosis analysis demonstrated the lowest cell viability and highest apoptosis in combination therapy, compared to three monotherapies (P<0.005). In in-vivo experiments, ultrasound imaging detected the smallest relative tumor volume for the combination therapy, compared to other monotherapies (P<0.005). In both in-vitro and in-vivo experiments, ICG-based interventional optical imaging detected a significantly decreased SI in combination therapy (P<0.005), which was confirmed by the “gold standard” optical/X-ray imaging (P<0.05). Pathologic/laboratory examinations further confirmed the significantly decreased cell proliferation with Ki-67 staining, significantly increased apoptotic index with TUNEL assay, and significantly increased quantities of CD8 and CD80 positive cells with immunostaining in the combination therapy group, compared to other three control groups (P<0.005). We present a new interventional oncology technique, interventional optical imaging-monitored RFH-enhanced oncolytic immunotherapy, which may open new avenues to effectively manage those patients with larger, irregular and unresectable malignancies, not only in liver but also the possibility in other organs.
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影响因子：
2.5
作者：
Schaafsma, Boudewijn E.;Mieog, J. Sven D.;Hutteman, Merlijn;Van der Vorst, Joost R.;Kuppen, Peter J. K.;Lowik, Clemens W. G. M.;Frangioni, John V.;Van de Velde, Cornelis J. H.;Vahrmeijer, Alexander L.
通讯作者：
Vahrmeijer, Alexander L.
影响因子：
11.2
作者：
Kan X;Zhou G;Zhang F;Ji H;Zheng H;Chick JFB;Valji K;Zheng C;Yang X
通讯作者：
Yang X
影响因子：
4
作者：
Hwang JE;Kim SH;Jin J;Hong JY;Kim MJ;Jung SH;Shim HJ;Bae WK;Hwang EC;Kim JW;Shin SS;Jeong O;Park YK;Cho SH;Chung IJ
通讯作者：
Chung IJ
影响因子：
19.7
作者：
Shi, Yaoping;Zhang, Feng;Yang, Xiaoming
通讯作者：
Yang, Xiaoming
DOI：
10.1002/cnm.3286
发表时间：
2019-12-23
影响因子：
2.1
作者：
Causin, Paola;Lupieri, Marina G.;Weishaeupl, Rada-M.
通讯作者：
Weishaeupl, Rada-M.