Institute of Microbiology AS CR, v.v.i., Videnska 1083, CZ-142 20, Prague 4, Czech Republic.
Curr Pharm Biotechnol. 2012 Jun;13(8):1446-73. doi: 10.2174/138920112800784835.
Bacterial toxins share the ability to enter host cells to target various intracellular proteins and to modulate host immune responses. Over the last 20 years, toxins and their mutated variants, as well as live attenuated bacteria, have been exploited for vaccination and immunotherapy of various infectious, malignant and autoimmune diseases. The ability of Bordetella pertussis adenylate cyclase toxin to translocate its adenylate cyclase domain across the host cell membrane, as well as the pathways of intracellular trafficking of Bacillus anthracis lethal and edema toxins, Shigella dysenteriae shiga toxin or Escherichia coli shiga-like toxin, have been repeatedly exploited for the delivery of antigenic epitopes into host cells and for stimulation of antigen-specific T cell responses. Similarly, E. coli α-hemolysin, or effector proteins of Yersinia and Salmonella secreted by the type III secretion systems, were used to facilitate the delivery of fused heterologous proteins or peptides for antigenic presentation. Vibrio cholerae cholera toxin, E. coli heat-labile enterotoxin, B. pertussis pertussis toxin or the Cry1A protein of Bacillus thuringiensis have shown a great potential to act as adjuvants and to stimulate mucosal as well as systemic immune responses. The immunotherapeutic potential of some toxins, like Clostridium perfringens perfringolysin O, Streptococcus intermedius intermedilysin, or Streptococcus pneumoniae pneumolysin needs to be evaluated further. The Bordetella adenylate cyclase toxoid used as a vaccine delivery tool, or Corynebacterium diphtheriae diphtheria toxin and Pseudomonas aeruginosa exotoxin A-based immunotoxins, are currently in various phases of clinical trials for cancer immunotherapy, as are some antigen-delivering Salmonella and Listeria monocytogenes strains.
细菌毒素具有进入宿主细胞靶向各种细胞内蛋白并调节宿主免疫反应的能力。在过去的 20 年中，毒素及其突变变体以及减毒活细菌已被用于各种感染性、恶性和自身免疫性疾病的疫苗接种和免疫治疗。百日咳博德特氏菌腺苷酸环化酶毒素将其腺苷酸环化酶结构域穿过宿主细胞膜的能力，以及炭疽杆菌致死毒素和水肿毒素、志贺氏痢疾杆菌志贺毒素或大肠杆菌志贺样毒素的细胞内运输途径，已被反复用于将抗原表位递送到宿主细胞中并刺激抗原特异性 T 细胞反应。同样，大肠杆菌α-溶血素或 Yersinia 和 Salmonella 通过 III 型分泌系统分泌的效应蛋白，也被用于促进融合的异源蛋白或肽的递呈以进行抗原呈递。霍乱弧菌霍乱毒素、大肠杆菌不耐热肠毒素、百日咳博德特氏菌百日咳毒素或苏云金芽孢杆菌的 Cry1A 蛋白已显示出作为佐剂的巨大潜力，可刺激黏膜和全身免疫反应。一些毒素（如产气荚膜梭菌 perfringolysin O、中间链球菌 intermedilysin 或肺炎链球菌 pneumolysin）的免疫治疗潜力需要进一步评估。作为疫苗传递工具使用的博德特氏菌腺苷酸环化酶类毒素，或白喉棒状杆菌白喉毒素和铜绿假单胞菌外毒素 A 为基础的免疫毒素，目前正在癌症免疫治疗的各个临床试验阶段，一些携带抗原的沙门氏菌和李斯特菌菌株也是如此。
