Mengesha Asferd, Dubois Ludwig, Chiu Roland K, Paesmans Kim, Wouters Bradly G, Lambin Philippe, Theys Jan
University of Maastricht, Department of Radiation Oncology (MAASTRO), GROW Research Institute, Maastricht, The Netherlands.
Front Biosci. 2007 May 1;12:3880-91. doi: 10.2741/2357.
Bacterial-based tumor-targeted therapy is an area of growing interest and holds promise for the treatment of solid tumors. Upon systemic administration, various types of non-pathogenic obligate anaerobes and facultative anaerobes have been shown to infiltrate and selectively replicate within solid tumors. The tumor specificity is based upon the unique physiology of solid tumors, which is often characterized by regions of hypoxia and necrosis. Prokaryotic vectors can be safely administered and their potential to deliver therapeutic proteins has been demonstrated in a variety of preclinical models. Although the amount of clinical experience with bacterial vectors is limited to date, the available data clearly demonstrated the feasibility of bacterial-mediated therapy in humans. There are several issues however that are still unknown and remain major challenges. In this review, using Clostridium and modified Salmonella as prototypical agents, we will discuss the major advantages, challenges and shortcomings of bacterial systems for tumor-specific therapy. In addition, we will highlight the requirements needed to advance the approach into clinical trials.
基于细菌的肿瘤靶向治疗是一个越来越受关注的领域，对实体瘤的治疗具有广阔前景。全身给药后，已证明多种类型的非致病性专性厌氧菌和兼性厌氧菌可在实体瘤内浸润并选择性复制。肿瘤特异性基于实体瘤独特的生理学特性，其通常以缺氧和坏死区域为特征。原核载体可以安全给药，并且它们递送治疗性蛋白质的潜力已在多种临床前模型中得到证实。尽管迄今为止细菌载体的临床经验有限，但现有数据清楚地证明了细菌介导疗法在人类中的可行性。然而，仍有几个问题尚不清楚，仍然是重大挑战。在本综述中，我们将以梭菌和改良沙门氏菌作为典型制剂，讨论用于肿瘤特异性治疗的细菌系统的主要优点、挑战和缺点。此外，我们将强调推进该方法进入临床试验所需的条件。
