Lichtor Terry, Glick Roberta P, Tarlock Katherine, Moffett Shannon, Mouw Elizabeth, Cohen Edward P
Department of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen Institute for Medical Research, Chicago, IL 60612, USA.
Cancer Gene Ther. 2002 May;9(5):464-9. doi: 10.1038/sj.cgt.7700459.
We found previously that mice injected intracerebrally (i.c.) with a mixture of malignant cells and allogeneic fibroblasts genetically engineered to secrete interleukin-2 (IL-2) survived longer than mice in various control groups. The primary goal of this study was to determine if an established i.c. glioma (Gl261) or breast carcinoma (SB-5b) could be treated by injection of IL-2-secreting allogeneic fibroblasts into the tumor region. As an additional objective, these results were compared with the effectiveness of injecting IL-2-secreting allogeneic fibroblasts prior to the introduction of the tumor cells as a means of preventing the development of an i.c. glioma or breast carcinoma. The results demonstrated that treatment of mice bearing an established i.c. glioma or breast carcinoma with IL-2-secreting allogeneic fibroblasts resulted in a prolonged survival. Furthermore, the results demonstrate a significant delay (P<.005) in the development of glioma in the animals treated with either allogeneic nonsecreting or IL-2-secreting fibroblasts prior to introduction of tumor cells. In addition, 50% of the animals pretreated with IL-2-secreting allogeneic fibroblasts injected subsequently with Gl261 glioma cells did not develop a tumor, whereas all of the animals injected with glioma cells alone and 92% of those treated with nonsecreting fibroblasts eventually died. Evidence also exists that long-term immunity was established in the treated animals because there was a significant prolongation of survival in comparison to naïve controls (P<.01) for those animals without evidence of glioma that previously had been immunized with treatment cells when challenged again with tumor cells. In a parallel experiment, 62% of the animals pretreated with nonsecreting allogeneic fibroblasts and 75% of the animals pretreated with allogeneic IL-2-secreting fibroblasts subsequently injected with SB-5b breast carcinoma cells did not develop tumors. The results indicate that IL-2-secreting allogeneic fibroblasts can be effective in the treatment of an established brain tumor. These data also suggest that i.c. injection of allogeneic IL-2-secreting fibroblasts is effective in prevention of the development of a brain tumor when the fibroblasts are introduced into the same site where the tumor is subsequently injected.
我们之前发现，向脑内（i.c.）注射恶性细胞与经基因工程改造以分泌白细胞介素-2（IL-2）的同种异体成纤维细胞混合物的小鼠，其存活时间比各个对照组的小鼠更长。本研究的主要目的是确定，通过向肿瘤区域注射分泌IL-2的同种异体成纤维细胞，是否能够治疗已形成的脑内胶质瘤（Gl261）或乳腺癌（SB-5b）。作为一个额外的目标，将这些结果与在引入肿瘤细胞之前注射分泌IL-2的同种异体成纤维细胞作为预防脑内胶质瘤或乳腺癌发生的方法的有效性进行比较。结果表明，用分泌IL-2的同种异体成纤维细胞治疗患有已形成的脑内胶质瘤或乳腺癌的小鼠，可延长其存活时间。此外，结果表明，在用同种异体非分泌型或分泌IL-2的成纤维细胞在引入肿瘤细胞之前进行治疗的动物中，胶质瘤的发生有显著延迟（P<0.005）。另外，预先用分泌IL-2的同种异体成纤维细胞处理、随后注射Gl261胶质瘤细胞的动物中，50%未发生肿瘤，而所有单独注射胶质瘤细胞的动物以及92%用非分泌型成纤维细胞处理的动物最终死亡。也有证据表明，在接受治疗的动物中建立了长期免疫，因为与未接触过肿瘤细胞的幼稚对照组相比（P<0.01），那些之前用治疗细胞免疫过且再次受到肿瘤细胞攻击时没有胶质瘤证据的动物存活时间显著延长。在一项平行实验中，预先用非分泌型同种异体成纤维细胞处理的动物中有62%、预先用分泌IL-2的同种异体成纤维细胞处理的动物中有75%，随后注射SB-5b乳腺癌细胞后未发生肿瘤。结果表明，分泌IL-2的同种异体成纤维细胞可有效治疗已形成的脑肿瘤。这些数据还表明，当将同种异体分泌IL-2的成纤维细胞注射到随后注射肿瘤的同一部位时，脑内注射该细胞可有效预防脑肿瘤的发生。
