DC疫苗对人免疫重建荷人膀胱癌NOD／SCID小鼠的抑瘤作用

Antitumor efficiency of DC vaccine in human bladder cancer-bearing NOD/ SCID mice with reconstituted human immune system

目的探讨DC疫苗对人免疫重建荷人膀胱癌NOD／SCID小鼠的抑瘤作用。方法从健康人外周血中分离单个核细胞（peripheral blood mononuclearcell，PBMC），经体外诱导培养获取树突状细胞（dendritic cell，Dc），并负载人膀胱癌EJ细胞裂解物中提取的肿瘤抗原制备DC疫苗。20只NOD／SCID小鼠腹腔注射人PBMC、皮下接种EJ细胞建立人免疫重建荷人膀胱癌动物模型，随机分为实验组（DC—EJ组）和对照组（DC组）；DC—EJ组腹腔注射DC疫苗，DC组腹腔注射DC，观察肿瘤生长和小鼠存活情况，检测荷瘤小鼠血清中人IFN-γ的含量，移植瘤组织中人T细胞、Dc的浸润情况。结果Dc—EJ组小鼠移植瘤生长缓慢，小鼠生存时间延长。实验组小鼠血清中人IFN-γ分泌显著高于对照组（P〈0．05），肿瘤组织中均见CD3、CD4、CD8T细胞和成熟DC浸润。结论负载人膀胱肿瘤抗原的DC疫苗能有效抑制人免疫重建NOD／SCID小鼠体内移植瘤的生长，为膀胱癌的免疫治疗提供了实验依据。

We aimed to evaluate the antitumor efficiency of DC vaccine in human bladder cancer-bearing NOD/SCID mice with reconstituted human immune system. We isolated mononuclear cells from healthy human peripheral blood, and in vitro inducted the peripheral blood mononuclear cells （PBMCs） for obtaining dendritic cells （DCs）. Then the DCs were loaded with the tumor antigen acquired from human EJ bladder cancer cell lysate for preparing DC vaccine. Human bladder cancer-bearing NOD/SCID mice with reconstituted human immune system model was established by intraperitoneal injection of human PBMCs and subcutaneous inoculation with human bladder cancer cell line EJ. Twenty NOD/SCID model mice were randomly divided into experimental group （DC-EJ group） and control group （DC group） of equal number. DC vaccines were injected intraperitoneally in DC- EJ group, and DCs were injected intraperitoneally in control group. We observed the tumor growth and mice survival. Also serum IFN-γ human T lymphocytes cells and mature DCs in transplanted tumor were detected in tumor-bearing mice. In DC-EJ group, the mouse transplanted tumor grew slowly and survival period of tumor bearing mice was prolonged as compared with the control group; the IFN-γ levels in DC-EJ group was significantly higher than that of control group （P〈0.05）. CD3, CD4, CD8 T lymphocytes and mature DC infiltration were all found in tumor tissues. The above results indicate that DC vaccine loaded with the bladder tumor antigen could effectively inhibit transplanted tumor to grow in NOD/SCID mice with reconstituted human immune system, which provides the experimental evidence for immunotherapy of bladder carcinoma.