Roth J C, Curiel D T, Pereboeva L
Department of Medicine, Division of Human Gene Therapy, The Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL 35294-2172, USA.
Gene Ther. 2008 May;15(10):716-29. doi: 10.1038/gt.2008.38. Epub 2008 Mar 27.
Use of cells as therapeutic carriers has increased in the past few years and has developed as a distinct concept and delivery method. Cell-based vehicles are particularly attractive for delivery of biotherapeutic agents that are difficult to synthesize, have reduced half-lives, limited tissue penetrance or are rapidly inactivated upon direct in vivo introduction. Initial studies using cell-based approaches served to identify some of the key factors for the success of this type of therapeutic delivery. These factors include the efficiency of cell loading with a therapeutic payload, the means of cell loading and the nature of therapeutics that cells can carry. However, one important aspect of cell-based delivery yet to be fully investigated is the process of actual delivery of the cell payload in vivo. In this regard, the potential ability of cell carriers to provide site-specific or targeted delivery of therapeutics deserves special attention. The present review focuses on a variety of targeting approaches that may be utilized to improve cell-based therapeutic delivery strategies. The different aspects of targeting that can be applied to cell vehicles will be discussed, including physical methods for directing cell distribution, intrinsic cell-mediated homing mechanisms and the feasibility of engineering cells with novel targeting mechanisms. Development of cell targeting strategies will further advance cell vehicle applications, broaden the applicability of this delivery approach and potentiate therapeutic outcomes.
在过去几年中,将细胞用作治疗载体的情况有所增加,并已发展成为一种独特的概念和递送方法。基于细胞的载体对于递送难以合成、半衰期缩短、组织穿透性有限或直接体内引入后迅速失活的生物治疗药物特别有吸引力。最初使用基于细胞方法的研究旨在确定这类治疗递送成功的一些关键因素。这些因素包括用治疗性负载加载细胞的效率、细胞加载方式以及细胞能够携带的治疗药物的性质。然而,基于细胞递送的一个尚未充分研究的重要方面是细胞负载在体内的实际递送过程。在这方面,细胞载体提供治疗药物的位点特异性或靶向递送的潜在能力值得特别关注。本综述重点关注可用于改进基于细胞的治疗递送策略的各种靶向方法。将讨论可应用于细胞载体的靶向的不同方面,包括指导细胞分布的物理方法、内在的细胞介导归巢机制以及用新型靶向机制改造细胞的可行性。细胞靶向策略的发展将进一步推进细胞载体的应用,拓宽这种递送方法的适用性并增强治疗效果。