Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.
Immunology and Immunotherapy Program, Center for Applied Medical Research, University of Navarra, Avenida Pío XII, 55, 31008, Pamplona, Spain.
J Vasc Interv Radiol. 2019 Jul;30(7):1098-1105. doi: 10.1016/j.jvir.2019.02.023. Epub 2019 May 14.
To evaluate the therapeutic efficacy of irreversible electroporation (IRE) combined with the intratumoral injection of the immunogenic adjuvant poly-ICLC (polyinosinic-polycytidylic acid and poly-L-lysine, a dsRNA analog mimicking viral RNA) inmediately before IRE.
Mice and rabbits bearing hepatocellular carcinoma tumors (Hepa.129 and VX2 tumor models, respectively) were treated with IRE (2 pulses of 2500V), with poly-ICLC, or with IRE + poly-ICLC combination therapy. Tumor growth in mice was monitored using a digital caliper and by computed tomography in rabbits.
Intratumoral administration of poly-ICLC immediately before IRE elicited shrinkage of Hepa.129 cell-derived tumors in 70% of mice, compared to 30% and 26% by poly-ICLC or IRE alone, respectively (P = .0004). This combined therapy induced the shrinkage of VX-2-based hepatocellular carcinoma tumors in 40% of rabbits, whereas no response was achieved by either individual treatment (P = .045). The combined therapy activated a systemic antitumor response able to inhibit the growth of other untreated tumors.
IRE treatment, immediately preceded by the intratumoral administration of an immunogenic adjuvant such as poly-ICLC, might enhance the antitumor effect of the IRE procedure. This combination might facilitate the induction of a long-term systemic response to prevent tumor relapses and the appearance of metastases.
评估不可逆电穿孔（IRE）联合肿瘤内注射免疫佐剂聚肌胞（聚肌苷酸-聚胞苷酸和聚赖氨酸，一种模拟病毒 RNA 的双链 RNA 类似物）即刻治疗肝癌的疗效。
分别使用 HCC129 细胞来源的肝癌荷瘤小鼠和 VX2 肿瘤荷瘤兔模型，接受 IRE（2 个 2500V 脉冲）、聚肌胞或 IRE 联合聚肌胞治疗。在小鼠中，通过数字卡尺和兔 CT 监测肿瘤生长。
IRE 治疗前即刻肿瘤内注射聚肌胞，使 70%的 Hepa.129 细胞来源的肿瘤缩小，而聚肌胞或 IRE 单独治疗的肿瘤缩小率分别为 30%和 26%（P =.0004）。这种联合治疗使 40%的兔 VX2 肝癌肿瘤缩小，而单独治疗则没有反应（P =.045）。联合治疗激活了全身性抗肿瘤反应，能够抑制其他未治疗肿瘤的生长。
IRE 治疗前即刻肿瘤内注射免疫佐剂（如聚肌胞）可能增强 IRE 治疗的抗肿瘤效果。这种联合治疗可能有助于诱导长期的全身性反应，以防止肿瘤复发和转移的发生。
