肿瘤细胞治疗研究
英文原题：Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off-the-shelf versatile tumor delivery vehicle.
靶向癌基因驱动癌症中的可操作突变和免疫肿瘤学的发展是影响癌症治疗范式并导致精准肿瘤学出现的两大显著革命。
靶向癌基因驱动癌症中的可操作突变以及免疫肿瘤学的发展，是影响癌症治疗范式并促成精准肿瘤学出现的两大显著革命。然而，肿瘤间和肿瘤内异质性正是这两个精准癌症治疗领域面临的主要挑战。换言之，在患有特定类型癌症的患者中寻找一个通用的标志物或通路是具有挑战性的。因此，针对单一标志或通路使用单一靶向治疗药物，对于对抗肿瘤异质性而言并不会有效。间充质干细胞（MSCs）具备用于细胞治疗的有利特性，包括其低免疫原性、固有的肿瘤趋向性、易于分离以及多向分化潜能。MSCs 可以负载多种化疗药物和溶瘤病毒。这些内在特征与基因操作的可能性相结合，使其成为一种多功能的肿瘤递送载体，可用于在体内选择性地将多种化疗和生物治疗药物递送至肿瘤部位。MSCs 可作为生物工厂，在肿瘤部位局部生产化学或生物抗癌剂。MSC 介导的免疫治疗可以促进免疫治疗药物在肿瘤部位的特异性持续释放，并使得无需反复全身给予高治疗剂量即可达到治疗浓度。尽管使用 MSC 在各种癌症治疗策略中的临床前研究激发了热情，但将 MSCs 转化为临床应用仍面临严峻挑战。本文以批判性视角综述了评估MSCs作为选择性肿瘤递送工具在各种癌症治疗方法中的临床前和临床研究，包括基因治疗、免疫治疗和化疗。随后，讨论了能够提高MSC肿瘤靶向效力并克服其在肿瘤部位低定位相关挑战的新型纳米技术和生物工程方法。
Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor-tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC-mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.
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