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目的 体内外观察多种细胞因子和 (或 )肿瘤相关抗原 (tumorallogenicantigen ,TAA)刺激的正常人树突状细胞 (DC)诱导免疫效应细胞对BEL 740 2的生长抑制。方法 体外分别用人GM CSF、IL 4、TNFα、BEL 740 2TAA和人IL 2刺激正常人DC和去DC的单个核细胞 (免疫效应细胞 ) ,5～ 6d后混合培养DC和免疫效应细胞 1～ 2d。体外实验时效应细胞分无DC刺激组 (A0组 )、细胞因子培养和DC刺激组 (A1组 )、细胞因子和TAA培养的DC刺激组 (A2组 )。体内实验时 ,裸鼠分为 3组 :预防组 (Ⅱ ) ,于接种BEL 740 2前 1～ 2d天给DC激活的免疫效应细胞 ;治疗组 (Ⅲ ) ,待全部裸鼠移植瘤长出时给DC激活的免疫效应细胞 ;组Ⅱ、Ⅲ于给予DC激活免疫效应细胞后再间断给予DC培养上清液 3～6d。对照组 (Ⅰ )给等量的 164 0培养液。结果 多细胞因子体外可刺激DC发生扩增并高表达B7分子。体外实验中最大杀伤效率 :A2组为 81% ,A1组为 68.1% ,A0组为 3 .5 %。体内实验中 :组Ⅰ和组Ⅲ第 12d时 12例全部发生移植瘤 ;组Ⅱ观察 3 0d时 ,6例有 1例发生移植瘤 ,观察 45d时 ,仍只有 1例发生移植瘤 ,组Ⅰ、Ⅱ相差有非常显著意义 (P =0 .0 0 466) ;在给予DC激活的免疫效应细胞后的第 45d处死所有裸鼠并称瘤体的重量 ,组Ⅰ、Ⅱ、Ⅲ比较相差有非常?
Objective To observe the growth inhibition of BEL 740 2 induced by immune effector cells in normal human dendritic cells (DCs) stimulated by various cytokines and / or tumor-associated antigens (TAA) both in vitro and in vivo. Methods Human monocytes (immune effector cells) were stimulated with human GM CSF, IL 4, TNFα, BEL 740 2TAA and human IL 2 in vitro. DCs and immune effector cells were mixed for 1 ~ 2 days . In vitro experiments, the effector cells were divided into DC stimulation group (A0 group), cytokine culture and DC stimulation group (A1 group), cytokine and TAA DC stimulation group (A2 group). In vivo experiments, nude mice were divided into three groups: preventive group (Ⅱ), DC-activated immune effector cells 1 day to 2 days before inoculation of BEL 740 2; treatment group (Ⅲ), when all nude mice grew To DC-activated immune effector cells; group Ⅱ, Ⅲ DC immunocompetent effector cells were given after discontinuation of DC culture supernatant 3 ~ 6d. The control group (I) gave an equal volume of 164 0 broth. Results Multiple cytokines stimulated DCs to proliferate in vitro and overexpress B7 molecules. The maximum killing efficiency in vitro was 81% in group A2, 68.1% in group A1 and 3.5% in group A0. In vivo, allograft tumors occurred in 12 cases on the 12th day in group Ⅰ and group Ⅲ. In the group Ⅱ, 1 case of transplantation tumor occurred on the 30th day. Only 1 case of transplantation tumor was observed on the 45th day. (P = 0.06046). All the nude mice were sacrificed on the 45th day after giving DC-activated immune effector cells and the weight of the tumor was not significantly different between groups Ⅰ, Ⅱ and Ⅲ.