Department of Surgery, University of California, San Diego, CA 92111, USA.
Curr Opin Biotechnol. 2011 Dec;22(6):917-23. doi: 10.1016/j.copbio.2011.03.009. Epub 2011 Apr 15.
A paradigm change in the treatment of cancer is urgently needed. Bacteria offer many advantages, including natural cytotoxity, motility, chemotaxis and a relative large genome to manipulate for tumor targeting. Salmonella, Clostridium, Bifodobacterium and Escherichia coli have been shown to control tumor growth and promote survival in animal models. We have developed an effective bacterial cancer therapy by engineering Salmonella typhimurium amino acid auxotrophs which grow in viable as well as necrotic areas of tumors, but not normal tissue. The S. typhimurium A1-R mutant, which is auxotrophic for leu-arg, is tumor-seeking and has antitumor efficacy against the major types of cancer. The approach described here is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy.
癌症的治疗迫切需要范式转变。细菌具有许多优势，包括天然细胞毒性、运动性、趋化性和相对较大的基因组，可用于肿瘤靶向操作。沙门氏菌、梭菌、双歧杆菌和大肠杆菌已被证明可控制动物模型中的肿瘤生长并促进存活。我们通过工程化鼠伤寒沙门氏菌氨基酸营养缺陷型来开发有效的细菌癌症疗法，这些缺陷型在肿瘤的存活和坏死区域生长，但不在正常组织中生长。鼠伤寒沙门氏菌 A1-R 突变体是亮氨酸-精氨酸营养缺陷型，具有寻瘤性，对主要类型的癌症具有抗肿瘤功效。与需要与毒性化疗结合使用的先前细菌肿瘤治疗策略相比，这里描述的方法是一个重大改进。
