Antitumor effects of a xenogeneic survivin bone marrow derived dendritic cell vaccine against murine GL261 gliomas
Antitumor effects of a xenogeneic survivin bone marrow derived dendritic cell vaccine against murine GL261 gliomas
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DOI：
10.1007/s00262-006-0138-6
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发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Fenstermaker, Robert A.
中科院分区：
文献类型：
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作者：
Ciesielski, Michael J.;Apfel, Lisa;Fenstermaker, Robert A.
Survivin是凋亡抑制蛋白家族的一员。神经胶质瘤和许多其他肿瘤高水平表达生存素;而正常的完全分化的细胞通常不表达生存素。因此，生存素代表了癌症疫苗治疗的肿瘤特异性靶点。已经表明，对存活素疫苗产生MHC-I限制性细胞免疫应答是可能的。为了研究小鼠和人生存素蛋白之间的免疫原性差异，我们接种C57 BL/6小鼠与骨髓树突状细胞（BMDC）转染的表达载体含有小鼠和人生存素基因。与单独转染载体的BMDCs相比，表达截短的人生存素蛋白的BMDCs疫苗接种的小鼠产生了针对皮下GL 261胶质瘤细胞的细胞毒性T淋巴细胞，并且表现出延长的无瘤存活（P < 0.01）。虽然用脑内GL 261细胞攻击的小鼠的存活率增加，但没有观察到治愈。相反，完全抵抗皮下肿瘤攻击的接种小鼠对脑内GL 261再攻击具有抗性。转染全长人生存素分子的BMDCs在延长生存期方面比表达全长鼠生存素基因的BMDCs更有效（P=0.0175）。因此，人类和小鼠序列之间的异种差异可能被利用来开发更具免疫原性的肿瘤疫苗。
Survivin is a member of the inhibitor of apoptosis protein family. Gliomas and many other tumors express survivin at high levels; whereas, normal fully differentiated cells generally do not. Therefore, survivin represents a tumor-specific target for cancer vaccine therapy. It has been shown that it is possible to produce a MHC-I-restricted cellular immunologic response to survivin vaccines. To study differences in immunogenicity between murine and human survivin proteins, we vaccinated C57BL/6 mice with bone marrow dendritic cells (BMDC) transfected with expression vectors containing the murine and human survivin genes. Mice vaccinated with BMDCs expressing a truncated human survivin protein developed cytotoxic T lymphocyte to subcutaneous GL261 glioma cells and exhibited prolonged tumor-free survival compared to mice vaccinated with BMDCs transfected with vector alone (P < 0.01). While mice challenged with intracerebral GL261 cells had increased survival, no cures were observed. In contrast, vaccinated mice that fully resisted subcutaneous tumor challenge were rendered resistant to intracerebral GL261 re-challenge. BMDCs transfected with the full-length human survivin molecule were significantly more effective at prolonging survival than BMDCs expressing the full-length murine survivin gene (P=0.0175). Therefore, xenogeneic differences between human and murine sequences might be exploited to develop more immunogenic tumor vaccines.