Beck Alain, Dumontet Charles, Joubert Nicolas
Institut de Recherche Pierre Fabre, Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160 Saint Julien-en-Genevois, France.
Cancer Research Center of Lyon (CRCL), Inserm 1052/CNRS, 69000 Lyon, France - Université de Lyon, 69000 Lyon, France - Hospices Civils de Lyon, 69000 Lyon, France.
Med Sci (Paris). 2019 Dec;35(12):1043-1053. doi: 10.1051/medsci/2019228. Epub 2020 Jan 6.
An Antibody-Drug Conjugate (armed antibody) is a vectorized chemotherapy that results from the grafting of a cytotoxic agent on a monoclonal antibody via a judiciously designed spacer arm. ADCs have made considerable progress in 10 years. In 2009, only gemtuzumab ozogamicin (Mylotarg) was used clinically. In 2019, 4 other ADCs have been approved and more than 80 others are in active clinical trials. The second part of this review will focus on new emerging strategies to address ADCs drawbacks and attempt to broaden their therapeutic window. Finally, combinations with conventional chemotherapy or checkpoint inhibitors will be discussed, in the pursuit to make Antibody-Drug Conjugates the embodiment of Paul Ehrlich's dream of the magic bullet.
抗体药物偶联物(武装抗体)是一种载体化化疗药物,它通过精心设计的间隔臂将细胞毒性剂嫁接到单克隆抗体上而产生。抗体药物偶联物在过去十年中取得了长足进展。2009年,仅有吉妥珠单抗奥唑米星(麦罗塔)用于临床。2019年,又有4种其他抗体药物偶联物获批,另有80多种正处于积极的临床试验中。本综述的第二部分将聚焦于应对抗体药物偶联物缺点的新出现策略,并尝试拓宽其治疗窗口。最后,将讨论与传统化疗或检查点抑制剂的联合使用,以期使抗体药物偶联物成为保罗·埃尔利希“神奇子弹”梦想的化身。