Abbina Srinivas, Siren Erika M J, Moon Haisle, Kizhakkedathu Jayachandran N
ACS Biomater Sci Eng. 2018 Nov 12;4(11):3658-3677. doi: 10.1021/acsbiomaterials.7b00514. Epub 2017 Oct 4.
The introduction of cell-based therapies has provided new and unique strategies to treat many diseases and disorders including the recent approval of CAR-T cell therapy for the leukemia. Cell surface engineering is a methodology in which the cell surface is tailored to modulate cellular function and interactions. In addition to genetic engineering of cell surface proteins, a wide array of robust, innovative and elegant approaches have been developed to selectively target the cell surface. In this review, we will introduce the leading strategies currently used in cell surface engineering including broadly reactive chemical ligations and physical associations as well as more controlled approaches as demonstrated in genetic, enzymatic and metabolic engineering. Prominent applications of these strategies for cell-based therapies will be highlighted including targeted cell death, control over stem cell fate, immunoevasion, blood transfusion and the delivery of cells to target tissues. Advances will be focused specifically on cells which are the most promising in generating cell-based therapeutics including red blood cells, white blood cells (lymphocytes, macrophages), stem cells (multipotent and pluripotent), islet cells, cancer cells, and endothelial cells.
基于细胞的疗法的引入为治疗包括最近获批用于白血病的嵌合抗原受体T细胞(CAR-T)疗法在内的多种疾病和病症提供了全新且独特的策略。细胞表面工程是一种对细胞表面进行改造以调节细胞功能和相互作用的方法。除了对细胞表面蛋白进行基因工程改造外,还开发了一系列强大、创新且巧妙的方法来选择性地靶向细胞表面。在本综述中,我们将介绍目前细胞表面工程中使用的主要策略,包括广泛反应性的化学连接和物理缔合,以及在基因、酶和代谢工程中展示的更具可控性的方法。将重点介绍这些策略在基于细胞的疗法中的突出应用,包括靶向细胞死亡、对干细胞命运的控制、免疫逃避、输血以及将细胞递送至靶组织。进展将特别聚焦于在生成基于细胞的治疗方法方面最具潜力的细胞,包括红细胞、白细胞(淋巴细胞、巨噬细胞)、干细胞(多能和全能干细胞)、胰岛细胞、癌细胞和内皮细胞。