在小鼠肿瘤模型中,术中用改良的自体肿瘤细胞进行皮下或脾内接种可提高生存率。
Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model.
作者信息
Dietrich Arne, Stockmar Christoph, Aust Gabriela, Endesfelder Susan, Guetz Anke, Sack Ulrich, Schoenfelder Manfred, Hauss Johann
机构信息
Clinic for Abdominal, Vascular, Thoracic and Transplant Surgery, Leipzig University, Chirurgische Klinik II, Liebigstr. 20, 04103 Leipzig, Germany.
出版信息
J Cancer Res Clin Oncol. 2006 Jun;132(6):379-88. doi: 10.1007/s00432-005-0073-5. Epub 2006 Jan 4.
PURPOSE
We investigated the effect of intraoperative intrasplenic or subcutaneous vaccination with modified tumor cells on tumor progression in a mouse model.
METHODS
Pre-established B16 melanomas on C57/Bl6 mice were surgically removed; mice were vaccinated intraoperatively with B16 cells transfected with an IL-12-encoding pRSC construct, the empty plasmid, or B16 frozen cells. Cells were given either intrasplenically or subcutaneously. Intrasplenic effects of vaccination were examined along with survival data. Mice without tumor recurrence underwent a second tumor implantation.
RESULTS
Animals administered IL-12 pRSC cells showed significant alterations in the spleen, such as higher percentages of (activated) CD4+ and CD8+ T cells and tumor-specific CD4+ T cells among splenocytes. The tumor recurrence rate after resection ranged from 13 to 36%. Cases with recurrent tumors in particular benefited in all therapy groups, resulting in enhanced (tumor-free) survival, reduced tumor growth and lower metastasis rates. Following macroscopic complete tumor resection, the optimum outcome resulted from vaccination with IL-12 pRSC cells into the spleen and subcutaneously administered frozen cells. Survival times were enhanced in all therapy groups after tumor reimplantation, although results were not significant.
CONCLUSIONS
Intraoperative whole-cell vaccination with autologous tumor cells yields promising data, and could be considered as a future option in adjuvant cancer therapy.
目的
我们在小鼠模型中研究了术中脾脏内或皮下接种经修饰的肿瘤细胞对肿瘤进展的影响。
方法
手术切除C57/Bl6小鼠预先建立的B16黑色素瘤;术中给小鼠接种用编码IL-12的pRSC构建体转染的B16细胞、空质粒或B16冻存细胞。细胞通过脾脏内或皮下注射给予。同时检查接种的脾脏内效应以及生存数据。无肿瘤复发的小鼠进行第二次肿瘤植入。
结果
给予IL-12 pRSC细胞的动物脾脏出现显著变化,如脾细胞中(活化的)CD4+和CD8+ T细胞以及肿瘤特异性CD4+ T细胞的百分比更高。切除术后肿瘤复发率为13%至36%。特别是复发肿瘤的病例在所有治疗组中均受益,导致(无瘤)生存期延长、肿瘤生长减缓以及转移率降低。在肉眼下完全切除肿瘤后,脾脏内接种IL-12 pRSC细胞和皮下注射冻存细胞的联合治疗效果最佳。肿瘤再植入后所有治疗组的生存时间均延长,尽管结果不显著。
结论
术中用自体肿瘤细胞进行全细胞接种产生了有前景的数据,可被视为辅助癌症治疗的未来选择。