Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
BMC Cancer. 2013 Jan 29;13:38. doi: 10.1186/1471-2407-13-38.
Interleukin-12 (IL-12) based radiosensitization is an effective way of tumor treatment. Local cytokine production, without systemic shedding, might provide clinical benefit in radiation treatment of sarcomas. Therefore, the aim was to stimulate intratumoral IL-12 production by gene electrotransfer of plasmid coding for mouse IL-12 (mIL-12) into the tumors, in order to explore its radiosensitizing effect after single or multiple intratumoral gene electrotransfer.
Solid SA-1 fibrosarcoma tumors, on the back of A/J mice, were treated intratumorally by mIL-12 gene electrotransfer and 24 h later irradiated with a single dose. Treatment effectiveness was measured by tumor growth delay and local tumor control assay (TCD(50) assay). With respect to therapeutic index, skin reaction in the radiation field was scored. The tumor and serum concentrations of cytokines mIL-12 and mouse interferon γ (mIFNγ) were measured. Besides single, also multiple intratumoral mIL-12 gene electrotransfer before and after tumor irradiation was evaluated.
Single intratumoral mIL-12 gene electrotransfer resulted in increased intratumoral but not serum mIL-12 and mIFNγ concentrations, and had good antitumor (7.1% tumor cures) and radiosensitizing effect (21.4% tumor cures). Combined treatment resulted in the radiation dose-modifying factor of 2.16. Multiple mIL-12 gene electrotransfer had an even more pronounced antitumor (50% tumor cures) and radiosensitizing (86.7% tumor cures) effect.
Single or multiple intratumoral mIL-12 gene electrotransfer resulted in increased intratumoral mIL-12 and mIFNγ cytokine level, and may provide an efficient treatment modality for soft tissue sarcoma as single or adjuvant therapy to tumor irradiation.
白细胞介素-12（IL-12）为基础的放射增敏是肿瘤治疗的有效方法。局部细胞因子的产生，而不是全身脱落，可能为肉瘤放射治疗提供临床益处。因此，本研究的目的是通过基因电转移质粒编码的小鼠白细胞介素-12（mIL-12）到肿瘤中，刺激肿瘤内 IL-12 的产生，以探讨其在单次或多次肿瘤内基因电转移后的放射增敏作用。
在 A/J 小鼠背部的实体 SA-1 纤维肉瘤肿瘤中，通过 mIL-12 基因电转移进行肿瘤内治疗，24 小时后给予单次剂量照射。通过肿瘤生长延迟和局部肿瘤控制测定（TCD（50）测定）来测量治疗效果。关于治疗指数，对放射野内的皮肤反应进行评分。测量肿瘤和血清中细胞因子 mIL-12 和小鼠干扰素 γ（mIFNγ）的浓度。除了单次治疗，还评估了肿瘤照射前后多次肿瘤内 mIL-12 基因电转移的效果。
单次肿瘤内 mIL-12 基因电转移导致肿瘤内而不是血清中 mIL-12 和 mIFNγ 浓度增加，具有良好的抗肿瘤（7.1%肿瘤治愈）和放射增敏作用（21.4%肿瘤治愈）。联合治疗导致放射剂量修正因子为 2.16。多次 mIL-12 基因电转移具有更显著的抗肿瘤（50%肿瘤治愈）和放射增敏（86.7%肿瘤治愈）作用。
单次或多次肿瘤内 mIL-12 基因电转移导致肿瘤内 mIL-12 和 mIFNγ 细胞因子水平增加，可能为软组织肉瘤提供一种有效的治疗方式，可作为肿瘤照射的单一或辅助治疗。
