A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas.
A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas.
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一种由人骨髓来源的间充质干细胞递送的新型双特异性免疫毒素，以靶向恶性胶质瘤的血管和血管生成拟态
DOI：
10.2147/dddt.s79475
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Zhang Y;Sun X;Huang M;Ke Y;Wang J;Liu X
背景在过去的几年里，免疫毒素已被证明是一个非常有前途的治疗工具，脑恶性肿瘤，如胶质瘤。人骨髓间充质干细胞（humanmesenchymalstemcells，hMSCs）对肿瘤组织具有趋化性。然而，双特异性免疫毒素在恶性胶质瘤中的作用仍然未知。本研究的目的是探讨双特异性免疫毒素在人类恶性胶质瘤中的作用。材料与方法本研究利用脱氧核糖核酸改组和克隆技术构建了VEGF 165-ephrin A1-PE 38 KDEL双特异性免疫毒素。VEGF 165-ephrin A1-PE 38 KDEL经hMSCs转染小鼠恶性胶质瘤。在体内研究了双特异性免疫毒素对胶质瘤源性血管和血管生成拟态的影响，以阐明免疫毒素抗肿瘤作用的分子机制。结果体外实验中，转染hMSCs对胶质瘤细胞系U87和U251的细胞活力有明显的抑制作用，且呈剂量依赖性（P<0.01）。在体内，瘤内注射工程化hMSC可有效抑制恶性胶质瘤肿瘤模型中的肿瘤生长。结论hMSCs分泌的双特异性免疫毒素为临床治疗恶性胶质瘤提供了新的策略。
Background In previous years, immunotoxins have been shown to be a greatly promising therapeutic tool for brain malignancies, such as gliomas. Human mesenchymal stem cells (hMSCs) exhibit tropism to tumor tissue. However, the effect of bispecific immunotoxins in malignant gliomas is still unknown. The aim of this study was to investigate the function of bispecific immunotoxins in human malignant gliomas. Materials and methods In the present study, the bispecific immunotoxin VEGF165-ephrin A1-PE38KDEL was established using deoxyribonucleic acid shuffling and cloning techniques. The VEGF165-ephrin A1-PE38KDEL was delivered by hMSCs to mouse malignant gliomas. The effects of the bispecific immunotoxins on glioma-derived blood vessels and vasculogenic mimicry to elucidate the molecular mechanisms underlying the antitumorigenic effects of immunotoxins were examined in vivo. Results In vitro, transfected hMSCs significantly inhibited the cell viability of gliomas cell lines U87 and U251 in a dose-dependent manner compared with untransfected hMSCs (P<0.01). In vivo, the intratumoral injection of engineered hMSCs was effective at inhibiting tumor growth in a malignant glioma tumor model. Conclusion The bispecific immunotoxin secreted from hMSCs acts as a novel strategy for improving treatment options for malignant gliomas in the clinic.