Infectious Disease Division, Department of Medicine.
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook.
Curr Opin Infect Dis. 2019 Jun;32(3):210-216. doi: 10.1097/QCO.0000000000000539.
This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of current clinical trials.
Monoclonal antibody (mAb) therapy is becoming increasingly promising in the infectious disease field. Though bacterial exotoxins continue to be a mainstay of mAb targets, searches for protein targets on the surface of bacteria have uncovered new mechanisms of antibody-mediated action against bacteria. Additionally, surveys of the polysaccharide serotype prevalence among antibiotic-resistant bacterial populations have yielded opportunities to leverage human selective pressures to our clinical advantage. Several mAb candidates are progressing through clinical development with great promise, especially those with structures altered to provide maximum benefit. Although other clinical trials have recently proved unsuccessful, these failures and lessons from immune profiling provide opportunities to understand how vulnerabilities of certain targets may change in different disease states.
Despite the hurdles of identifying effective targets and understanding how mAbs provide protection within different infections, we show that the progress made in these fields is a positive indication of mAbs becoming more widely accepted as the future for treating bacterial infections.
本文重点介绍了治疗细菌性疾病的单克隆抗体的最新研究进展,包括临床前进展和当前临床试验的状况。
单克隆抗体(mAb)治疗在传染病领域越来越有前途。尽管细菌外毒素仍然是 mAb 靶标的主要成分,但对细菌表面蛋白靶标的研究揭示了抗体介导的抗细菌作用的新机制。此外,对抗生素耐药菌群体中多糖血清型流行情况的调查为利用人类选择压力为我们的临床优势提供了机会。几种 mAb 候选药物正在进行临床开发,前景非常广阔,特别是那些结构经过修饰以提供最大益处的候选药物。尽管最近的其他临床试验都失败了,但这些失败以及免疫分析的经验教训为我们提供了机会,以了解某些靶标的脆弱性在不同疾病状态下可能会如何变化。
尽管在确定有效靶点和了解 mAb 在不同感染中的保护作用方面存在困难,但我们表明,在这些领域取得的进展表明,mAb 作为治疗细菌感染的未来,越来越被广泛接受。