Jiang Xiao-bing, Lu Xiao-ling, Hu Peng, Liu Ru-en
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Vaccine. 2009 Oct 19;27(44):6210-6. doi: 10.1016/j.vaccine.2009.08.002. Epub 2009 Aug 20.
The purpose of the present study was to evaluate the therapeutic efficacy of glioma lysate-pulsed DCs in combination with plasmid DNA vector encoding the murine interferon-induced protein of 10kDa (IP-10 or CXCL10) gene. Mouse models of brain glioma (GL261) were treated with combining glioma lysate-pulsed DCs with direct intratumoral injection of a nonviral plasmid DNA vector encoding the murine IP-10 gene. The survival of mice bearing GL261 glioma was observed. Enzyme-linked immuno-spot assay was used to determine the frequency of brain-infiltrating lymphocytes (BILs) capable of responding to GL261. Cytolytic T lymphocyte (CTL) response was measured by cytotoxic assay, vessel density and tumor cell proliferation were observed by immunostaining, and tumor apoptosis was determined by TUNEL staining. The results revealed that the combination therapy groups showed more significantly enhanced anti-tumor activity, attraction of lymphocytes into tumor tissues, apoptosis of tumor cells, and reduced neovascularization, cell proliferation, and developed a strong CTL response in these mice. In summary, the therapy of glioma lysate-pulsed DCs combined with the IP-10 gene has significant synergistic effect against glioma.
本研究的目的是评估胶质瘤裂解物脉冲树突状细胞（DCs）与编码小鼠10kDa干扰素诱导蛋白（IP-10或CXCL10）基因的质粒DNA载体联合使用的治疗效果。将胶质瘤裂解物脉冲DCs与直接瘤内注射编码小鼠IP-10基因的非病毒质粒DNA载体相结合，对脑胶质瘤（GL261）小鼠模型进行治疗。观察携带GL261胶质瘤的小鼠的存活情况。采用酶联免疫斑点分析来确定能够对GL261产生反应的脑浸润淋巴细胞（BILs）的频率。通过细胞毒性测定来测量细胞毒性T淋巴细胞（CTL）反应，通过免疫染色观察血管密度和肿瘤细胞增殖情况，并通过TUNEL染色确定肿瘤细胞凋亡情况。结果显示，联合治疗组在这些小鼠中表现出更显著增强的抗肿瘤活性、淋巴细胞向肿瘤组织的募集、肿瘤细胞凋亡以及新生血管形成减少、细胞增殖减少，并产生了强烈的CTL反应。总之，胶质瘤裂解物脉冲DCs与IP-10基因联合治疗对胶质瘤具有显著的协同作用。
