Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia; Veterinary Faculty, University of Ljubljana, Gerbiceva 60, 1000 Ljubljana, Slovenia.
Veterinary Faculty, University of Ljubljana, Gerbiceva 60, 1000 Ljubljana, Slovenia.
Int Immunopharmacol. 2023 Jul;120:110274. doi: 10.1016/j.intimp.2023.110274. Epub 2023 May 20.
The combined treatment of electrochemotherapy (ECT) and interleukin-12 (IL-12) gene electrotransfer (GET) has already been used in clinical studies in dogs to treat various histological types of spontaneous tumors. The results of these studies show that the treatment is safe and effective. However, in these clinical studies, the routes of administration of IL-12 GET were either intratumoral (i.t.) or peritumoral (peri.t.). Therefore, the objective of this clinical trial was to compare the two IL-12 GET routes of administration in combination with ECT and their contribution to the enhanced ECT response. Seventy-seven dogs with spontaneous mast cell tumors (MCTs) were divided into three groups: one treated with a combination of ECT + GET peri. t. (29 dogs), the second with the combination of ECT + GET i.t. (30 dogs), and the third with ECT alone (18 dogs). In addition, immunohistochemical studies of tumor samples before treatment and flow cytometry of peripheral blood mononuclear cells (PBMCs) before and after treatment were performed to determine any immunological aspects of the treatment. The results showed that local tumor control was significantly better in the ECT + GET i.t. group (p < 0.050) than in the ECT + GET peri.t. or ECT groups. In addition, disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT + GET i.t. group than in the other two groups (p < 0.050). The data on local tumor response, DFI, and PFS were consistent with immunological tests, as we detected an increased percentage of antitumor immune cells in the blood after treatment in the ECT + GET i.t. group, which also indicated the induction of a systemic immune response. In addition, we did not observe any unwanted severe or long-lasting side effects. Finally, due to the more pronounced local response after ECT + GET i.t., we suggest that treatment response assessment should be performed at least two months after treatment, which meets the iRECIST criteria.
电化学疗法 (ECT) 和白细胞介素 12 (IL-12) 基因电转移 (GET) 的联合治疗已在治疗各种自发肿瘤的组织学类型的犬科临床研究中使用。这些研究的结果表明该治疗是安全有效的。然而，在这些临床研究中，IL-12 GET 的给药途径是肿瘤内 (i.t.) 或肿瘤周围 (peri.t.)。因此，本临床试验的目的是比较 ECT 联合两种 IL-12 GET 给药途径及其对增强 ECT 反应的贡献。77 只患有自发性肥大细胞瘤 (MCT) 的狗被分为三组：一组接受 ECT + GET peri.t. 联合治疗（29 只狗），第二组接受 ECT + GET i.t. 联合治疗（30 只狗），第三组仅接受 ECT 治疗（18 只狗）。此外，在治疗前对肿瘤样本进行免疫组织化学研究，并在治疗前后对外周血单核细胞 (PBMC) 进行流式细胞术，以确定治疗的任何免疫学方面。结果表明，ECT + GET i.t. 组的局部肿瘤控制明显优于 ECT + GET peri.t. 或 ECT 组（p < 0.050）。此外，ECT + GET i.t. 组的无病间隔 (DFI) 和无进展生存期 (PFS) 明显长于其他两组（p < 0.050）。局部肿瘤反应、DFI 和 PFS 的数据与免疫测试一致，因为我们在 ECT + GET i.t. 组中检测到治疗后血液中抗肿瘤免疫细胞的百分比增加，这也表明诱导了全身性免疫反应。此外，我们没有观察到任何不良的严重或长期副作用。最后，由于 ECT + GET i.t. 后的局部反应更明显，我们建议在治疗后至少两个月进行治疗反应评估，这符合 iRECIST 标准。
