抗体药物偶联物作为肿瘤学各实体的靶向治疗方法。
Antibody-Drug Conjugates as a Targeted Therapeutic Approach Across Entities in Oncology.
机构信息
Department of Oncology, Gastroenterology, Hepatology, Pulmonology, University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany, Leipzig, Germany; Department of Hematology, Cell therapy und Hemostaseology, University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany, Leipzig, Germany; Rudolf Boehm Institute of Pharmacology and Toxicology, Independent Department of Clinical Pharmacology, Medical Faculty, University of Leipzig, Comprehensive Cancer Center Central Germany, Leipzig, Germany.
出版信息
Dtsch Arztebl Int. 2023 May 12;120(19):329-336. doi: 10.3238/arztebl.m2023.0093.
BACKGROUND
Cancer is no longer treated on the basis of its histological lineage alone; more and more drugs are being developed that are directed toward specific molecular and immunological features. Monoclonal antibodies are one type of selectively acting therapeutic agent. As part of this development, antibody-drug conjugates ("ADCs") have been approved in recent years for the treatment of hematologic and solid malignancies.
METHODS
This review is based on pertinent articles retrieved by a selective search in PubMed, as well as on papers presented at international congresses of specialist societies such as the European Society for Medical Oncology, the American Society of Clinical Oncology, and the American Association for Cancer Research, and information published on the websites of the European Medicines Agency, the Food and Drug Administration, and the German Joint Federal Committee.
RESULTS
The efficacy of the nine ADCs currently approved in the European Union (as of 12/2022) is derived from technical improvements in the conjugation process, the introduction of novel linkers for the covalent binding of cytotoxic agents to the Fc portion of the antibody, and the development of new, potent cytotoxic agents. Compared to conventional cancer therapies, the approved ADCs improve treatment outcomes with respect to tumor remission, time to tumor progression and, in some cases, overall survival by specifically channeling cytotoxic agents into the malignant target cells and thereby limiting, at least to some extent, the exposure of healthy tissue to adverse effects. Various potential side effects still require attention, including venous occlusive disease, pneumonitis, ocular keratopathy, and skin rash. The development of effective ADCs requires the identification of tumor-selective targets to which ADCs can bind.
CONCLUSION
ADCs are a novel category of drugs for the treatment of cancer. Their approval is mainly, but not exclusively, based on the favorable findings of randomized, controlled phase III trials. ADCs are already helping to improve the outcomes of treatment for cancer.
背景
癌症的治疗不再仅仅基于其组织学谱系，越来越多的药物被开发出来，针对特定的分子和免疫学特征。单克隆抗体是一种选择性作用的治疗剂。作为这一发展的一部分，近年来，抗体药物偶联物（“ADC”）已被批准用于治疗血液系统和实体恶性肿瘤。
方法
本综述基于在 PubMed 中进行选择性搜索获得的相关文章，以及在欧洲肿瘤内科学会、美国临床肿瘤学会和美国癌症研究协会等专业学会的国际大会上提交的论文，以及欧洲药品管理局、美国食品和药物管理局和德国联合联邦委员会网站上发布的信息。
结果
截至 2022 年 12 月，在欧盟批准的九种 ADC 的疗效源自于连接过程的技术改进，为将细胞毒性剂共价连接到抗体的 Fc 部分而引入的新型接头，以及新的、有效的细胞毒性剂的开发。与传统癌症治疗相比，批准的 ADC 通过将细胞毒性剂特异性地输送到恶性靶细胞，从而限制健康组织受到不良反应的暴露，在肿瘤缓解、肿瘤进展时间以及在某些情况下总生存方面改善治疗结果。各种潜在的副作用仍需要关注，包括静脉闭塞性疾病、肺炎、眼角膜病变和皮疹。有效的 ADC 的开发需要鉴定 ADC 可以结合的肿瘤选择性靶标。
结论
ADC 是治疗癌症的一类新型药物。它们的批准主要但不限于基于随机、对照 III 期试验的有利结果。ADC 已经有助于改善癌症治疗的结果。
Zotero 插件