Wang Cheng-Zhi, Kazmierczak Robert A, Eisenstark Abraham
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Cancer Research Center, Columbia, MO 65201, USA.
Cancer Research Center, Columbia, MO 65201, USA; University of Missouri-Columbia, Columbia, MO 65201, USA.
Int J Microbiol. 2016;2016:5678702. doi: 10.1155/2016/5678702. Epub 2016 Apr 14.
Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such as Salmonella, Listeria, Escherichia, and Clostridium have proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeutic Salmonella models, the most intensively studied bacterial genus in this field. One of these Salmonella models is our Salmonella enterica serovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypes in vitro and in vivo, and what is currently known about the mechanisms by which they target and destroy tumors.
最近，由于分子生物学、细胞生物学和微生物学的进展，基于细菌的肿瘤治疗研究重新成为焦点。许多细菌，如沙门氏菌、李斯特菌、大肠杆菌和梭菌，已被证明具有肿瘤靶向性，在某些情况下甚至具有肿瘤破坏表型。此外，通过与化疗药物和放射性制剂等其他治疗方法联合使用，癌症的细菌临床治疗也得到了改善。合成生物学技术也推动了新型基于细菌的癌症治疗方法的发展。然而，关于细菌介导的肿瘤靶向和破坏机制的基本问题仍在不断阐明。在这篇综述中，我们重点关注三种用于肿瘤治疗的沙门氏菌模型，这是该领域研究最深入的细菌属。其中一种沙门氏菌模型是我们的鼠伤寒沙门氏菌LT2衍生菌株CRC2631，经过基因工程改造以尽量降低毒性，但最大限度地提高肿瘤靶向和破坏效果。另外两种是VNP20009和A1-R。我们比较了选择这些治疗候选菌株模型进行研究的方式、它们在体外和体内的肿瘤靶向和肿瘤破坏表型，以及目前已知的它们靶向和破坏肿瘤的机制。
