Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, North Carolina, Chapel Hill, 27599, USA.
Department of Neurosurgery, The University of North Carolina at Chapel Hill, North Carolina, Chapel Hill, 27599, USA.
Stem Cell Rev Rep. 2021 Dec;17(6):2025-2041. doi: 10.1007/s12015-021-10192-0. Epub 2021 Jun 17.
Despite the recent influx of immunotherapies and small molecule drugs to treat tumors, cancer remains a leading cause of death in the United States, in large part due to the difficulties of treating metastatic cancer. Stem cells, which are inherently tumoritropic, provide a useful drug delivery vehicle to target both primary and metastatic tumors. Intravenous infusions of stem cells carrying or secreting therapeutic payloads show significant promise in the treatment of cancer. Stem cells may be engineered to secrete cytotoxic products, loaded with oncolytic viruses or nanoparticles containing small molecule drugs, or conjugated with immunotherapies. Herein we describe these preclinical and clinical studies, discuss the distribution and migration of stem cells following intravenous infusion, and examine both the limitations of and the methods to improve the migration and therapeutic efficacy of tumoritropic, therapeutic stem cells.
尽管最近有免疫疗法和小分子药物涌入治疗肿瘤,但癌症仍然是美国主要的死亡原因,这在很大程度上是由于治疗转移性癌症的困难。干细胞本身具有肿瘤趋向性,为靶向原发性和转移性肿瘤提供了有用的药物递送载体。携带或分泌治疗有效载荷的干细胞静脉输注在癌症治疗中显示出巨大的前景。可以对干细胞进行工程改造以分泌细胞毒性产物,装载溶瘤病毒或含有小分子药物的纳米颗粒,或与免疫疗法结合。本文描述了这些临床前和临床研究,讨论了静脉输注后干细胞的分布和迁移,并检查了肿瘤趋向性治疗性干细胞的迁移和治疗效果的局限性和改进方法。