Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada.
Toxins (Basel). 2010 May;2(5):998-1018. doi: 10.3390/toxins2050998. Epub 2010 May 7.
Therapeutic agents targeting bacterial virulence factors are gaining interest as non-antibiotic alternatives for the treatment of infectious diseases. Clostridium difficile is a Gram-positive pathogen that produces two primary virulence factors, enterotoxins A and B (TcdA and TcdB), which are responsible for Clostridium difficile-associated disease (CDAD) and are targets for CDAD therapy. Antibodies specific for TcdA and TcdB have been shown to effectively treat CDAD and prevent disease relapse in animal models and in humans. This review summarizes the various toxin-specific antibody formats and strategies under development, and discusses future directions for CDAD immunotherapy, including the use of engineered antibody fragments with robust biophysical properties for systemic and oral delivery.
靶向细菌毒力因子的治疗剂作为治疗传染病的非抗生素替代品正受到关注。艰难梭菌是一种革兰阳性病原体,它产生两种主要的毒力因子,肠毒素 A 和 B(TcdA 和 TcdB),它们是导致艰难梭菌相关性疾病(CDAD)的原因,也是 CDAD 治疗的靶点。针对 TcdA 和 TcdB 的抗体已被证明可有效治疗 CDAD 并预防动物模型和人类疾病复发。本综述总结了正在开发的各种毒素特异性抗体形式和策略,并讨论了 CDAD 免疫疗法的未来方向,包括使用具有稳健生物物理特性的工程化抗体片段进行全身和口服递送。