Ranchon Florence, Chatelut Étienne, Lambert Juliette, Sesques Pierre, Thibault Constance, Madelaine Isabelle, Rioufol Catherine, Diéras Véronique, Cazin Jean-Louis
Hospices civils de Lyon, groupement hospitalier Sud, unité de pharmacie clinique oncologique, Pierre-Bénite, France; Université Lyon 1, EA 3738, CICLY centre pour l'innovation en cancérologie de Lyon, 69921 Lyon, Oullins cedex, France; Société française de pharmacie oncologique (SFPO), Paris, France.
Université Paul Sabatier, institut Claudius-Regaud, institut universitaire du cancer Toulouse - Oncopole ; CRCT, centre de recherche en cancérologie de Toulouse, Inserm U1037, Toulouse, France.
Bull Cancer. 2023 Dec;110(12):1343-1351. doi: 10.1016/j.bulcan.2023.07.009. Epub 2023 Oct 10.
Antibody Drug Conjugates (ADC) and bispecific antibodies are booming and were the subject of the scientific event proposed by the French Society of Oncological Pharmacy, October 13, 2022. An ADC is composed of the antibody targeting a receptor expressed on the tumor cell, the spacer making it possible to attach the cytotoxic to the antibody and to control its distribution in the body, and the cytotoxic. Therapeutic antibodies, monoclonal and conjugated, have particular pharmacokinetics. Unlike monoclonal antibodies for which the standard dose is most often fixed, this is expressed in mg/m (or mg/kg) and capped at 2m (or 100kg) for conjugates. The linked cytotoxics are powerful cytotoxics: mitotic spindle poisons (emtansine, monomethyl auristatin E or vedotin), topoisomerase I inhibitors (deruxtecan, SN 38) or antibiotics (ozogamicin). In senology, trastuzumab deruxtecan (anti-HER2) and sacituzumab govitecan (anti-Trop 2) are now modifying treatment standards for patients with metastatic breast cancer, respectively HER2 3X or HER2 low and triple negative. In metastatic bladder cancer, enfortumab vedotin (anti-nectin 4) is positioned as the 2nd line of treatment. Bispecific antibodies, on the other hand, are able to target two epitopes, an antigen specific to a tumor cell and one to an immune cell, allowing a bridge between the killer immune cells and the tumor cells. For lymphoma proliferation, many bispecific antibodies are in development. The most advanced are glofitamab, epcoritamab and mosunetuzumab, which target the CD20 of B lymphocytes and the CD3 of T lymphocytes. Bispecific antibodies are also emerging in the treatment of myeloma with teclistamab and elranatamab (anti-CD3 and anti-BCMA) or talquetamab (anti-GPRC5D and anti-CD3). Conjugated antibodies, and more recently bispecific antibodies, are potential game changers in cancer treatment and researchs are needed to improve their efficacy and safety.
抗体药物偶联物(ADC)和双特异性抗体正蓬勃发展,并且是法国肿瘤药学协会于2022年10月13日举办的科学活动的主题。一个ADC由靶向肿瘤细胞上表达的受体的抗体、使细胞毒性药物能够连接到抗体并控制其在体内分布的间隔物以及细胞毒性药物组成。治疗性抗体,包括单克隆抗体和偶联抗体,具有特殊的药代动力学。与标准剂量通常固定的单克隆抗体不同,偶联抗体的剂量以mg/m²(或mg/kg)表示,且上限为2m²(或100kg)。连接的细胞毒性药物是强效细胞毒性药物:有丝分裂纺锤体毒物(恩杂鲁胺、单甲基奥瑞他汀E或维布妥昔单抗)、拓扑异构酶I抑制剂(德曲妥珠单抗、SN 38)或抗生素(奥佐米星)。在乳腺病学中,曲妥珠单抗德曲妥珠单抗(抗HER2)和戈沙妥珠单抗(抗Trop 2)目前正在分别改变HER2 3+或HER2低表达以及三阴性转移性乳腺癌患者的治疗标准。在转移性膀胱癌中,恩沃利单抗(抗NECTIN 4)被定位为二线治疗药物。另一方面,双特异性抗体能够靶向两个表位,一个是肿瘤细胞特有的抗原,另一个是免疫细胞的抗原,从而在杀伤性免疫细胞和肿瘤细胞之间架起一座桥梁。对于淋巴瘤增殖,许多双特异性抗体正在研发中。最先进的是格罗菲他单抗、依泊妥单抗和莫苏奈妥单抗,它们靶向B淋巴细胞的CD20和T淋巴细胞的CD3。双特异性抗体在骨髓瘤治疗中也崭露头角,如替西他单抗和埃拉纳单抗(抗CD3和抗BCMA)或他喹他单抗(抗GPRC5D和抗CD3)。偶联抗体,以及最近出现的双特异性抗体,是癌症治疗中潜在的变革者,需要开展研究以提高它们的疗效和安全性。