Heller Loree C, Singh Julie S, Synowiec Jody C, Cherukuri Pavan Kumar, Phan Nhat, Shi Guilan, Jaroszeski Mark J, Otten Alex, Heller Richard
Department of Medical Engineering, University of South Florida, Tampa, FL 33612, USA.
Mol Ther Oncol. 2025 Aug 14;33(3):201035. doi: 10.1016/j.omton.2025.201035. eCollection 2025 Sep 18.
Interleukin-12 (IL-12) is a potent immune stimulator that induces the proliferation and activation of natural killer (NK) and T cells and the secretion of interferon (IFN)-γ. While IL-12 is an effective anti-cancer therapy, high concentrations may produce unwanted adverse effects or result in immune suppression. We previously demonstrated that intratumor delivery of a plasmid encoding IL-12 with gene electrotransfer (GET) induced local and systemic tumor control with no detected adverse effects. However, the shortcomings of standard GET are that high voltage is required and the lack of a delivery completion signal. We recently developed an improved system that overcomes these issues by incorporating sophisticated electrodes, mild heat application, and real time tissue impedance monitoring. In this study, we validated this advanced electrotransfer system. We compared the therapeutic efficacy of intratumor IL-12 GET in B16-f10 mouse melanomas delivered by standard and advanced technologies. Delivery with both standard and advanced electrotransfer reduced the tumor specific growth rate and increased survival. Our results demonstrated that therapeutic gene delivery can be achieved with a less intense pulse regimen.
白细胞介素-12（IL-12）是一种强效免疫刺激剂，可诱导自然杀伤（NK）细胞和T细胞的增殖与活化以及干扰素（IFN）-γ的分泌。虽然IL-12是一种有效的抗癌疗法，但高浓度可能会产生不良副作用或导致免疫抑制。我们之前证明，通过基因电穿孔（GET）将编码IL-12的质粒瘤内递送可诱导局部和全身肿瘤控制，且未检测到不良反应。然而，标准GET的缺点是需要高电压且缺乏递送完成信号。我们最近开发了一种改进系统，通过结合精密电极、温和加热应用和实时组织阻抗监测来克服这些问题。在本研究中，我们验证了这种先进的电穿孔系统。我们比较了通过标准技术和先进技术在B16-f10小鼠黑色素瘤中进行瘤内IL-12 GET的治疗效果。标准电穿孔和先进电穿孔递送均降低了肿瘤特异性生长率并提高了生存率。我们的结果表明，采用强度较低的脉冲方案即可实现治疗性基因递送。
