文章：

基因工程间充质干细胞：肿瘤根除免疫调节剂的靶向递送

Genetically engineered mesenchymal stem cells: targeted delivery of immunomodulatory agents for tumor eradication

原文发布日期：2020-05-18 

英文摘要：

Cancer immunotherapy emerged as a novel therapeutic option that employs enhanced or amended native immune system to create a robust response against malignant cells. The systemic therapies with immune-stimulating cytokines have resulted in substantial dose-limiting toxicities. Targeted cytokine immunotherapy is being explored to overcome the heterogeneity of malignant cells and tumor cell defense with a remarkable reduction of systemic side effects. Cell-based strategies, such as dendritic cells (DCs), fibroblasts or mesenchymal stem cells (MSCs) seek to minimize the numerous toxic side effects of systemic administration of cytokines for extended periods of time. The usual toxicities comprised of a vascular leak, hypotension, and respiratory insufficiency. Natural and strong tropism of MSCs toward malignant cells made them an ideal systemic delivery vehicle to direct the proposed therapeutic genes to the vicinity of a tumor where their expression could evoke an immune reaction against the tumor. Compared with other methods, the delivery of cytokines via engineered MSCs is safer and renders a more practical, and promising strategy. Large numbers of genes code for cytokines have been utilized to reengineer MSCs as therapeutic cells. This review highlights the recent findings on the cytokine gene therapy for human malignancies by focusing on MSCs application in cancer immunotherapy. 

摘要翻译： 

癌症免疫疗法作为一种新型治疗手段，通过增强或修饰天然免疫系统来建立对恶性细胞的强力应答。基于免疫刺激因子的全身性疗法曾导致严重的剂量限制性毒性。为克服恶性肿瘤细胞的异质性及肿瘤细胞防御机制，并显著降低全身性副作用，靶向细胞因子免疫疗法正在被积极探索。基于树突状细胞（DCs）、成纤维细胞或间充质干细胞（MSCs）的细胞策略，旨在长期减轻全身性细胞因子给药带来的多重毒副作用。常见毒性反应包括血管渗漏、低血压和呼吸功能不全。MSCs对恶性细胞具有天然强向性，使其成为理想的全身递送载体，能将治疗基因定向输送至肿瘤周边区域，通过基因表达激发抗肿瘤免疫反应。相较于其他方法，通过工程化MSCs递送细胞因子更安全、更实用，且具有更广阔的应用前景。大量细胞因子编码基因已被用于重构MSCs作为治疗性细胞。本综述重点探讨以MSCs在癌症免疫治疗中的应用为核心的细胞因子基因疗法用于人类恶性肿瘤的最新研究进展。

原文链接：

Genetically engineered mesenchymal stem cells: targeted delivery of immunomodulatory agents for tumor eradication