Interventional Oncolytic Immunotherapy with LTX-315 for Residual Tumor after Incomplete Radiofrequency Ablation of Liver Cancer.
Interventional Oncolytic Immunotherapy with LTX-315 for Residual Tumor after Incomplete Radiofrequency Ablation of Liver Cancer.
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肝癌是世界上最常见的恶性肿瘤之一，射频消融（RFA）是肝癌患者最喜欢的治疗方法。然而，不完全RFA经常发生在不规则和中等至较大（>3 cm）的肝脏肿瘤中。本研究的目的是验证LTX-315介入溶瘤免疫治疗肝癌不完全RFA后残留肿瘤的可行性。LTX-315在消融过程中通过电极插针注入肿瘤边缘，可以直接杀死肿瘤细胞并激活抗肿瘤免疫反应。这种治疗策略有助于创建清晰的消融肿瘤边缘。这项研究的证据可能为不规则和中大型肝癌RFA后预防残留肿瘤开辟新途径。目的：在兔模型中，研究使用LTX-315对VX 2肝肿瘤进行不完全射频消融（iRFA）后残留肿瘤进行介入溶瘤免疫治疗的可行性。研究方法：对于体外实验，用以下处理VX 2肿瘤细胞：（1）磷酸盐缓冲盐水、（2）射频热疗（RFH）、（3）LTX-315和（4）RFH加LTX-315。VX 2肝肿瘤iRFA后的残留肿瘤用以下物质处理：（1）磷酸盐缓冲盐水作为对照，（2）2 mg LTX-315和（3）4 mg LTX-315。用MTS法、荧光显微镜和流式细胞仪比较各组细胞的存活率和凋亡情况。超声成像用于随访肿瘤生长，并与光学成像和随后的组织学检查相关联。结果如下：对于体外实验，与其他三个组相比，MTS测定显示最低的细胞活力，荧光显微镜显示最少的存活细胞，并且凋亡分析显示联合处理组中凋亡细胞的百分比最高（p < 0.001）。对于体内实验，超声成像显示与其他两组相比，用4 mg LTX-315治疗的组中的肿瘤体积最小（p < 0.001）。光学成像和组织病理学分析显示在用4 mg LTX-315治疗的组中肿瘤完全坏死。与对照组相比，在用2 mg LTX-315治疗的组中，在残留肿瘤中观察到⑶ 8 + T细胞和HSP 70的显著增加和TcB的显著降低（p < 0.001）。结论：LTX-315介入溶瘤免疫治疗肝癌iRFA后残留肿瘤是可行的，这可能为预防中大型肝癌RFA后残留肿瘤开辟新途径。
Radiofrequency ablation (RFA) is a favorite treatment approach for patients with liver cancer, one of the most common malignancies worldwide. However, incomplete RFA often occurs in irregular and medium-to-larger (>3 cm) hepatic tumors. The aim of this study was to validate the feasibility of interventional oncolytic immunotherapy with LTX-315 for residual tumors after incomplete RFA of liver cancers. LTX-315, injected into tumor margins through the electrode prongs during the ablation procedure, can directly kill tumor cells and activate an anti-tumor immune response. This treatment strategy facilitated the creation of a clear ablated tumor margin. The evidence of this study may open up new avenues to prevent residual tumors after RFA of irregular and medium-to-large liver cancers. Objective: To investigate the feasibility of interventional oncolytic immunotherapy with LTX-315 for residual tumors after incomplete radiofrequency ablation (iRFA) of VX2 liver tumors in a rabbit model. Methods: For in vitro experiments, VX2 tumor cells were treated with: (1) phosphate buffered saline, (2) radiofrequency hyperthermia (RFH), (3) LTX-315, and (4) RFH plus LTX-315. The residual tumors after iRFA of VX2 liver tumors were treated with: (1) phosphate buffered saline served as control, (2) 2 mg LTX-315, and (3) 4 mg LTX-315. MTS assay, fluorescence microscopy, and flow cytometry were used to compare cell viabilities and apoptosis among different groups. Ultrasound imaging was used to follow up the tumor growth, which were correlated with the optical imaging and subsequent histology. Results: For in vitro experiments, compared with the other three groups, MTS assay demonstrated the lowest cell viability, fluorescence microscopy showed the least survival cells, and apoptosis analysis revealed the highest percentage of apoptosis cells in the combination treatment groups (p < 0.001). For in vivo experiments, ultrasound imaging showed the smallest tumor volume in the group with 4 mg LTX-315 therapy compared with the other two groups (p < 0.001). The optical imaging and histopathological analysis showed complete necrosis of the tumors in the group with 4 mg LTX-315 therapy. A significant increase of CD8+ T cells and HSP70 and a significant decrease of Tregs were observed in residual tumors in the group with 2 mg LTX-315 therapy compared with the control group (p < 0.001). Conclusion: Interventional oncolytic immunotherapy with LTX-315 for residual tumors after iRFA of liver cancer is feasible, which may open up new avenues to prevent residual tumors after RFA of intermediate-to-large liver cancers.
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影响因子：
5.8
作者：
Camilio, Ketil Andre;Berge, Gerd;Ravuri, Chandra Sekhar;Rekdal, Oystein;Sveinbjornsson, Baldur
通讯作者：
Sveinbjornsson, Baldur
影响因子：
19.7
作者：
Shi, Yaoping;Zhang, Feng;Yang, Xiaoming
通讯作者：
Yang, Xiaoming
影响因子：
11.5
作者：
Spicer, James;Marabelle, Aurelien;Rekdal, Oystein
通讯作者：
Rekdal, Oystein
影响因子：
7.2
作者：
Nestvold J;Wang MY;Camilio KA;Zinöcker S;Tjelle TE;Lindberg A;Haug BE;Kvalheim G;Sveinbjørnsson B;Rekdal Ø
通讯作者：
Rekdal Ø
影响因子：
4.7
作者：
Qian K;Chen M;Zhang F;Chick JFB;Ji H;Zheng C;Yang X
通讯作者：
Yang X