Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States.
Front Immunol. 2019 Jan 11;9:3084. doi: 10.3389/fimmu.2018.03084. eCollection 2018.
Despite decades of intensive attention directed to creation of genetically altered cells (e.g., as in development of chimeric antigen receptor (CAR) T-cells) and/or to achieve requisite accumulation of desired immunologic effectors (e.g., elaboration of virus-specific T cells, expansion of NK cells, differentiation of dendritic cells, isolation, and propagation of Tregs, etc.), there has been essentially no interest in the most fundamental of all hurdles: assuring tissue-specific delivery of administered therapeutic cells to sites where they are needed. With regards to use of CAR T-cells, the absence of information on the efficacy of cell delivery is striking, especially in light of the clear association between administered cell dose and adverse events, and the obvious fact that pertinent cell acquisition/expansion costs would be dramatically curtailed with more efficient delivery of the administered cell bolus. Herein, based on information garnered from studies of human leukocytes and adult stem cells, the logic underlying the use of cell surface glycoengineering to enforce E-selectin ligand expression will be conveyed in the context of how this approach offers strategies to enhance delivery of CAR T-cells to marrow and to tumor beds. This application of glycoscience principles and techniques with intention to optimize cell therapeutics is a prime example of the emerging field of "translational glycobiology."
尽管数十年来一直致力于创造基因改变的细胞（例如，开发嵌合抗原受体 (CAR) T 细胞）和/或实现所需免疫效应物的必要积累（例如，产生病毒特异性 T 细胞、扩增 NK 细胞、分化树突状细胞、分离和培养 Treg 等），但对于所有障碍中最基本的障碍几乎没有任何兴趣：确保给予的治疗性细胞在需要的部位特异性递送到组织中。就 CAR T 细胞的应用而言，细胞递送的疗效信息的缺乏是惊人的，尤其是考虑到给予的细胞剂量与不良事件之间的明确关联，以及明显的事实是，通过更有效的给予细胞剂量的传递，相关的细胞获取/扩增成本将大大降低。在此，基于从人类白细胞和成人干细胞研究中获得的信息，将根据该方法如何提供增强 CAR T 细胞向骨髓和肿瘤床递送到策略的背景，传达使用细胞表面糖基工程强制表达 E-选择素配体的基本原理。将糖科学原理和技术有意用于优化细胞治疗是“转化糖生物学”这一新兴领域的主要范例。
