【摘要】 目的:研究激发型4-1BB单抗(2A)联合凋亡肿瘤细胞负载的DC(AP-DC)疫苗在小鼠B细胞淋巴瘤免疫治疗中的作用。方法:凋亡小鼠B细胞淋巴瘤细胞A20负载的DC用来制备AP-DC。A20荷瘤小鼠分别被注射AP-DC、2A单抗或二者联合。观察肿瘤生长情况及小鼠生存期。流式细胞术检测免疫治疗后荷瘤鼠脾脏T细胞的表型和胞浆内细胞因子;3H-TdR掺入试验检测T细胞体外增殖能力;ELISA法检测荷瘤鼠血清和脾脏T细胞培养上清中IL-2、IFN-γ和IL-10含量。结果:应用激发型4-1BB单抗2A或AP-DC疫苗对荷瘤小鼠开展免疫治疗,可抑制肿瘤生长,延长荷瘤鼠生存期,获得12.5%或25%的肿瘤完全缓解率。但二者联合应用,治疗效果更好,可获得62.5%的肿瘤完全缓解率,并且荷瘤鼠可长期生存。联合治疗后荷瘤鼠脾脏T细胞体外增殖更为显著,CD4+IFN-γ+T细胞的比例也明显增加。IL-2和IFN-γ的分泌水平在联合治疗荷瘤鼠的血清和脾脏T细胞的培养上清中升高更明显,而IL-10的分泌则降低。结论:激发型4-1BB单抗和AP-DC在肿瘤免疫治疗中有协同作用。更多还原

【Abstract】 Objective:To investigate the immunotherapeutic role of agonistic mAb(2A) to 4-1BB molecule together with apoptotic tumor cell pulsed dendritic cell(AP-DC) vaccines in B cell lymphoma.Methods:Apoptotic B cell lymphoma cell line A20 pulsed DC was utilized to prepare AP-DC vaccine.A20 tumor bearing mice were injected with AP-DC vaccine,mAb-2A and AP-DC vaccine plus mAb-2A,respectively.The tumor growth in and survival of A20 bearing mice were measured.The phenotype and cytoplasmic cytokines of spleen T cells of A20 bearing mice after immunotherapy were analyzed by FCM.The proliferation of spleen T cells was tested by means of()~3H-TdR incorporation.ELISA was employed to determine the IL-2,IFN-γ and IL-10 levels in the serum and supernatant of cultured spleen T cells of A20 bearing mice.Results:The administration of agonistic mAb-2A or AP-DC vaccine inhibited tumor growth,prolonged the life-span of tumor bearing mice and induced 12.5% and 25% tumor complete remission respectively.The administration of agonistic mAb-2A plus AP-DC vaccine turned out to be the most effective,and obtained 62.5% tumor complete remission with long-term survival of A20 bearing mice.In combined therapeutic group mice,spleen T cells were more efficient to proliferate in vitro and the proportion of CD4~+IFN-γ~+T cells increased.IL-2 and IFN-γ levels in the serum and supernatant of cultured spleen T cells were more enhanced in combined therapeutic group mice than in other groups.In contrast,IL-10 level decreased.Conclusion:The agonistic mAb to 4-1BB molecule and AP-DC have synergistic roles in tumor immunotherapy.更多还原