University of Ljubljana, Veterinary Faculty, Small Animal Clinic, Cesta v Mestni log 47, 1000 Ljubljana, Slovenia.
Institute of Oncology Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia.
Res Vet Sci. 2019 Feb;122:40-49. doi: 10.1016/j.rvsc.2018.11.001. Epub 2018 Nov 12.
The aim of this study was to evaluate the safety and efficacy of the combination of electrochemotherapy (ECT) with bleomycin and gene electrotransfer (GET) of plasmid encoding canine interleukin 12 (IL-12) for the treatment of canine oral malignant melanoma (OMM). Our focus was to determine the effect of the treatment on achieving local tumor control and stimulation of an antitumor immune response. Nine dogs with histologically confirmed OMM stage I to III were included in a prospective, non-randomized study. The dogs were treated with a combination of cytoreductive surgery, ECT and IL-12 GET, which was repeated up to five times, depending on the clinical response to the treatment, evaluated according to the follow-up protocol (7, 14 and 28 days after, the last treatment). One month after treatment, the objective response (OR) rate was 67% (6/9). Median survival time (MST) was 6 months and, even though the disease progressed in 8/9 patients at the end of the observation period (2 to 22 months), four animals were euthanized due to tumor-unrelated reasons. In addition, we observed a decline in the percentage of regulatory T cells (T) in the peripheral blood in the course of the treatment, which could be attributed to a systemic antitumor response to IL-12 GET. The results of this study suggest that a combination of ECT and IL-12 GET may be beneficial for dogs with OMM, especially when other treatment approaches are not acceptable due to their invasiveness or cost.
本研究旨在评估电化学疗法(ECT)联合平阳霉素和犬白细胞介素 12(IL-12)质粒基因电转移(GET)治疗犬口腔恶性黑色素瘤(OMM)的安全性和疗效。我们的重点是确定该治疗方法对实现局部肿瘤控制和刺激抗肿瘤免疫反应的效果。9 只经组织学证实为 I 期至 III 期 OMM 的犬被纳入一项前瞻性、非随机研究。这些犬接受了包括细胞减灭手术、ECT 和 IL-12 GET 的联合治疗,根据随访方案(治疗后 7、14 和 28 天),根据临床反应重复治疗,最多可达 5 次。治疗后 1 个月,客观缓解率(OR)为 67%(6/9)。中位生存时间(MST)为 6 个月,尽管在观察期结束时(2 至 22 个月)8/9 例患者的疾病进展,但由于肿瘤无关原因,有 4 只动物被安乐死。此外,我们在治疗过程中观察到外周血中调节性 T 细胞(T)的百分比下降,这可能归因于 IL-12 GET 的全身性抗肿瘤反应。本研究结果表明,ECT 联合 IL-12 GET 可能对 OMM 犬有益,尤其是在由于其侵袭性或成本而不能接受其他治疗方法时。