激发型4-1BB单抗联合凋亡肿瘤细胞负载的树突状细胞在恶性肿瘤免疫治疗中的作用  

Roles of agonistic mAb against 4-1BB plus apoptotic tumor-loaded dendritic cells in malignant tumor′s immunotherapy

作　　者：李敏[1] 陈成[1] 古涛[1] 周桓[1] 张烽[1] 朱一蓓[1] 於葛华[1] 张学光[1] 顾宗江[1] 

机构地区：[1]苏州大学医学生物技术研究所免疫学教研室,苏州215007

出　　处：《中国免疫学杂志》2006年第7期640-644,649,共6页Chinese Journal of Immunology

基　　金：①本课题受国家自然科学基金项目(30271205);江苏省临床免疫学重点实验室基金资助

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。Objective： To investigate the immunotherapeutic role of agonistic mAb （2A） to 4-1 BB 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 ceils 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 remis- sion 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 ceils increased. IL-2 and IFN-γ levels in the serum and supernatant of cultured spleen T ceils 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.

关 键 词：树突状细胞 4-1BB分子 肿瘤免疫治疗 

分 类 号：Q254[生物学—细胞生物学] R392.1[医药卫生—免疫学]