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α-CD3单克隆抗体对肿瘤特异性T细胞的扩增和杀瘤活性的影响

EFFECT OF ANTI-CD3 MONOCLONAL ANTIBODY ON EXPANSION AND ANTI-TUMOR ACTIVITY OF TUMOR SPECIFIC T CELLS

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【作者】 俞红黄辉林云璐

【Author】 Yu Hong;Huang Hui;Lin Yunlu(Department of Immunology,School of Basic Medical Sciences,Shanghai Medical University,Shanghai 200032)

【机构】 上海医科大学基础医学院免疫学教研室

【摘要】 为寻找更有效的肿瘤过继性免疫治疗的方案,用α-CD3单克隆抗体(单抗)激活FBL-3红白血病肿瘤细胞免疫的小鼠脾细胞获取肿瘤特异性T细胞,并观察α-CD3单抗对肿瘤特异性T细胞的增殖、杀瘤活性及表型的影响。体外实验结果显示,免疫小鼠脾细胞经α-CD3单抗激活后,采用低剂量IL-2即可维持其长期高度的、持续的增殖;又培养过程中α-CD3单抗持续存在可大大促进其对肿瘤的特异性杀伤。细胞分型分析结果也支持了α-CD3单抗的持续存在对维持肿瘤特异性T细胞的抗瘤活性具有很重要的意义,是肿瘤过继免疫疗法中颇有前景的治疗方案。

【Abstract】 PURPOSE The changes on cell expansion and anti-tumor activity of mouse tumor-specific T cells activated by anti-CD3 monoclonal antibody(McAb) were investigated.The goal of this study is to find out more efficient method for tumor adoptive immunotherapy.METHODS Tumor-specific T cells from tumor-immunized mice were obtained by in vitro activation of anti-CD3 monoclonal antibody.The changes on cell expansion and anti-tumor activity as well as phenotype were studied.Four different culture modes were applied in this experiment:(1) cultured in anti-CD3 McAb alone(anti-CD3 group);(2) cultured in 20 000u/L rIL-2 alone(IL-2 group);(3) activated by anti-CD3 McAb for 48 hr and then cultured in 20 000u/L rIL-2 alone(CD3-IL-2 group);(4) activated by anti-CD3McAb for 48 hr and then cultured in CD3 McAb plus 20 000u/L rIL-2(CD3+IL-2 group).RESULTS The cells in CD3-IL-2 group and CD3+IL-2 group increased and expanded 780 folds and 610 folds respectively within 20 day.The maximum anti-tumor activities of both groups were 41.8% and 91.8% respectively on day 12.However,the continuous use of anti-CD3 McAb alone had neither proliferative effect nor anti-tumor activity.The IL-2group maintained a low level of proliferation within 20 days and showed its maximum anti-tumor activity of 30.2% on day 12.The study of cell phenotype by FACS analysis on day 6 indicated that>98% effective cells of both the CD3-IL-2 group and CD3+IL-2 group were Thy1.2+ cells.On day 20 Thy1.2+ cells of CD3+IL-2 group was still 98.8% while Thy1.2+ cell of CD3-IL-2 group was only 44.4%.There were also differences in CD4+ and CD8+ between the 2 groups.CONCLUSIONS The tumor-specific T cells cultured in the presence of the combination of anti-CD3 McAb and low dosed rIL-2 may facilitate a rapid expansion and long term maintenance of higher cytotoxicity.In general,this is a promising approach in tumor adoptive immunotherapy.

【基金】 国家自然科学基金
  • 【文献出处】 上海医科大学学报 ,ACTA ATADEMIAE MEDICINAE SHANGHAI , 编辑部邮箱 ,1996年02期
  • 【分类号】R394
  • 【被引频次】4
  • 【下载频次】57
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