Arsanis Biosciences, Vienna, Austria.
Arch Biochem Biophys. 2012 Oct 15;526(2):124-31. doi: 10.1016/j.abb.2012.06.001. Epub 2012 Jun 13.
Today's medicine has to deal with the emergence of multi-drug resistant bacteria, and is beginning to be confronted with pan-resistant microbes. This worsening inadequacy of the antibiotics concept, which has ruled infectious medicine in the last six decades creates an increasing unmet medical need that can be addressed by passive immunization. While past experience from the pre-antibiotic era with serum therapy was in many cases encouraging, antibacterial monoclonal antibodies have so far suffered high attrition rates in the clinic, generally from lack of efficacy. Yet, we believe that recent developments in a number of areas such as infectious disease pathogenesis research, translational medicine, mAb engineering, mAb manufacturing and rapid bedside diagnostics are converging to make the medium-term future permissive for antibacterial mAb development. Here, we review antibacterial mAb-based approaches that are or were in clinical development, and may potentially act as paradigms with regards to molecular targets, antibody formats and mode-of-action, pre-clinical validation and selection of most relevant patient populations, in order to increase the likelihood of successful product development in this field.
如今的医学必须应对多药耐药菌的出现，并开始面临泛耐药微生物。过去六十年主导传染病医学的抗生素概念的这种缺陷日益严重，导致未满足的医疗需求不断增加，而被动免疫可以解决这一问题。虽然过去在抗生素时代之前的血清疗法在许多情况下令人鼓舞，但抗菌单克隆抗体在临床上的损耗率一直很高，通常是因为缺乏疗效。然而，我们相信，传染病发病机制研究、转化医学、mAb 工程、mAb 制造和床边快速诊断等多个领域的最新进展正在汇聚，使得抗菌 mAb 开发的中期前景成为可能。在这里，我们回顾了处于临床开发或曾经处于临床开发阶段的基于抗菌 mAb 的方法，这些方法可能在分子靶点、抗体形式和作用模式、临床前验证以及选择最相关的患者群体方面成为范例，以增加该领域成功产品开发的可能性。
