Synergistic effect of a granulocyte-macrophage colony-stimulating factor-transduced tumor vaccine and systemic interleukin-2 in the treatment of murine colorectal cancer hepatic metastases
Synergistic effect of a granulocyte-macrophage colony-stimulating factor-transduced tumor vaccine and systemic interleukin-2 in the treatment of murine colorectal cancer hepatic metastases
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DOI：
10.1245/aso.2003.10.006
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发表时间：
2003-08-01
影响因子：
3.7
通讯作者：
Schulick, RD
中科院分区：
文献类型：
--
作者：
Jain, A;Slansky, JE;Schulick, RD
背景：粒细胞-巨噬细胞集落刺激因子转导的肿瘤细胞疫苗随着转移和初始接种间隔的增加，对癌症的有效性降低。方法：采用同基因结直肠癌系（CT26）与脾注射模型在BALB/c小鼠中产生肝转移。用辐照后的CT26细胞转导分泌粒细胞-巨噬细胞集落刺激因子作为疫苗。治疗组分别接种疫苗、全身白介素（IL-2）或两者兼用。肿瘤侵袭后21天检查肝脏是否有大体转移。用酶联免疫斑点法和细胞毒性T淋巴细胞法分析脾细胞对CT26的体外活性。结果：88%经疫苗和IL-2处理的小鼠在第21天无肿瘤(P <或等于。001 vs. control)。单独使用疫苗或IL-2治疗没有显著的治疗效果。在效应靶比为100、30和10时，同时接种疫苗和IL-2的小鼠脾细胞的CT26溶解比单独接种疫苗的小鼠脾细胞的CT26溶解更大（P < 0.05）。与单独接种疫苗的小鼠相比，这些小鼠的脾细胞在CT26肿瘤抗原AH1刺激下释放干扰素- γ更多（P = 0.05）。结论：全身性IL-2可增强肿瘤疫苗治疗小鼠微观结直肠癌肝转移的疗效。
Background: Granulocyte-macrophage colony-stimulating factor-transduced tumor cell vaccines are less effective against cancer as the interval between metastasis and the initial vaccination increases.Methods: Hepatic metastases were generated in BALB/c mice by using a syngeneic colorectal cancer line (CT26) with a splenic injection model. Irradiated CT26 cells transduced to secrete granulocyte-macrophage colony-stimulating factor were used as vaccine. Treatment groups received vaccine, systemic interleukin (IL-2), or both. Livers were examined for gross metastases 21 days after tumor challenge. Splenocytes were analyzed for in vitro activity against CT26 by using an enzyme-linked immunospot assay and a cytotoxic T lymphocyte assay.Results: Eighty-eight percent of mice treated with vaccines and IL-2 were tumor free on day 21 (P less than or equal to .001 vs. control). Treatment with vaccines or IL-2 alone did not result in a significant treatment effect. Splenocytes from mice treated with both vaccines and IL-2 showed greater CT26 lysis than splenocytes from mice treated with vaccines alone at effector:target ratios of 100, 30, and 10 (P < .05 for all). More splenocytes from these mice released interferon-gamma in response to stimulation with the CT26 tumor antigen AH1 compared with mice treated with vaccines alone (P = .05).Conclusions: Systemic IL-2 augments tumor vaccine efficacy in the treatment of microscopic murine colorectal hepatic metastases.