Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France.
Ecole du Val-de-Grâce, 75005 Paris, France.
Toxins (Basel). 2022 Feb 25;14(3):172. doi: 10.3390/toxins14030172.
Anthrax is an acute disease caused by the bacterium , and is a potential biowarfare/bioterrorist agent. Its pulmonary form, caused by inhalation of the spores, is highly lethal and is mainly related to injury caused by the toxins secretion. Antibodies neutralizing the toxins of are regarded as promising therapeutic drugs, and two are already approved by the Federal Drug Administration. We developed a recombinant human-like humanized antibody, 35PA83 6.20, that binds the protective antigen and that neutralized anthrax toxins in-vivo in White New Zealand rabbits infected with the lethal 9602 strain by intranasal route. Considering these promising results, the preclinical and clinical phase one development was funded and a program was started. Unfortunately, after 5 years, the preclinical development was cancelled due to industrial and scientific issues. This shutdown underlined the difficulty particularly, but not only, for an academic laboratory to proceed to clinical development, despite the drug candidate being promising. Here, we review our strategy and some preliminary results, and we discuss the issues that led to the no-go decision of the pre-clinical development of 35PA83 6.20 mAb. Our review provides general information to the laboratories planning a (pre-)clinical development.
炭疽是一种由细菌引起的急性疾病，也是一种潜在的生物战争/生物恐怖主义制剂。其肺部形式是由吸入孢子引起的，具有高度致命性，主要与毒素分泌引起的损伤有关。中和毒素的抗体被认为是有前途的治疗药物，其中两种已被美国联邦药物管理局批准。我们开发了一种重组人源化单克隆抗体 35PA83 6.20，它可以结合保护性抗原，并通过鼻腔途径在感染致死性 9602 菌株的新西兰白兔体内中和炭疽毒素。考虑到这些有希望的结果，该药物的临床前和一期临床试验得到了资助，并启动了一个项目。不幸的是，5 年后，由于工业和科学问题，临床前开发被取消。这一关闭突显了一个问题，即尽管候选药物很有前途，但对于一个学术实验室来说，要进行临床开发特别困难，但不仅仅如此。在这里，我们回顾了我们的策略和一些初步结果，并讨论了导致 35PA83 6.20 mAb 临床前开发失败的问题。我们的审查为计划（临床前）开发的实验室提供了一般信息。
