Dietrich Arne, Becherer Lars, Brinckmann Ute, Hauss Johann, Liebert Uwe G, Gütz Anke, Aust Gabriela
Clinic for Visceral, Thoracic, Vascular and Transplant Surgery, University of Leipzig, Leipzig, Germany.
Cancer Biother Radiopharm. 2006 Aug;21(4):333-41. doi: 10.1089/cbr.2006.21.333.
We investigated the effects of continuous cancer gene therapy including (antigen-presenting cell) (APC) engineering and local stimulation of the immune system.
Lewis lung carcinomas and B16 melanomas, intradermally established on C57/Bl6 mice, were shot using a gene gun every 4th day with a combination of plasmids. The first therapy group received plasmids coding the genes for interleukin (IL)-12 and IL-2. The second therapy group was treated with plasmids coding for B7.1 interferon-gamma (IFN-gamma)/IL-12 alternated by a plasmid coding IL-2. Control were mice without any therapy or treatment with the empty plasmid.
Gene therapy led to reduced tumor sizes in the therapy groups of both models (significant for the Lewis lung carcinoma). We found an enhanced survival and reduced tumor growth rate in the therapy groups; however, the effects were not significant. IL- 12/IL-2 therapy was more effective, compared to B7.1/IFN-gamma/IL-12 and IL-2. Cytokine gene transfer let to a significantly lower metastasis rate in Lewis lung carcinoma.
Continuous particle-mediated gene transfer is easy to handle and shows good results. Gene therapy combining the genes coding for IL-12 and IL-2 was superior to additional IFN-gamma/B7.1. APC engineering does not appear to be sufficient in these poorly antigenic tumors.
我们研究了包括（抗原呈递细胞）（APC）工程和局部免疫系统刺激在内的连续癌症基因治疗的效果。
在C57/Bl6小鼠皮内建立的Lewis肺癌和B16黑色素瘤，每隔4天用基因枪注射质粒组合。第一个治疗组接受编码白细胞介素（IL）-12和IL-2基因的质粒。第二个治疗组用编码B7.1、干扰素-γ（IFN-γ）/IL-12的质粒治疗，交替使用编码IL-2的质粒。对照组为未接受任何治疗或用空质粒治疗的小鼠。
基因治疗导致两个模型的治疗组肿瘤大小减小（对Lewis肺癌有显著意义）。我们发现治疗组的生存率提高，肿瘤生长速率降低；然而，效果不显著。与B7.1/IFN-γ/IL-12和IL-2相比，IL-12/IL-2治疗更有效。细胞因子基因转移使Lewis肺癌的转移率显著降低。
连续粒子介导的基因转移易于操作且效果良好。联合编码IL-12和IL-2基因的基因治疗优于额外的IFN-γ/B7.1。在这些低抗原性肿瘤中，APC工程似乎并不充分。
