Bouchard Hervé, Viskov Christian, Garcia-Echeverria Carlos
Natural Products and Protein Chemistry, Sanofi, 94403 Vitry-sur-Seine, France; Lead Generation to Compound Realization, Sanofi, 94403 Vitry-sur-Seine, France.
Lead Generation to Compound Realization, Sanofi, 94403 Vitry-sur-Seine, France.
Bioorg Med Chem Lett. 2014 Dec 1;24(23):5357-63. doi: 10.1016/j.bmcl.2014.10.021. Epub 2014 Oct 13.
Antibody-drug conjugates (ADCs) consist of cytotoxic drugs covalently linked to monoclonal antibodies directed to antigens differentially overexpressed in tumor cells. These loaded antibodies are expected to selectively deliver lethal cargoes to tumor cells and provide sustained clinical benefit to pre-selected cancer patients while, at the same time, minimizing systemic toxicity. Although on-target adverse events are not completely avoided and the true efficacy of these innovative agents still requires further clarification, proof-of-concept has already been achieved in clinical settings with immunoconjugates containing calicheamicin, auristatin or maytansine-based cytotoxic payloads. In this present article we review the characteristics of the preceding cytotoxic platforms and their chemical conjugation approaches.
抗体药物偶联物（ADCs）由与单克隆抗体共价连接的细胞毒性药物组成，这些单克隆抗体针对肿瘤细胞中差异过表达的抗原。这些负载抗体有望将致命的药物选择性地递送至肿瘤细胞，并为预先选定的癌症患者提供持续的临床益处，同时将全身毒性降至最低。尽管无法完全避免靶向不良事件，且这些创新药物的真正疗效仍需进一步阐明，但含有卡奇霉素、奥瑞他汀或美登素类细胞毒性载荷的免疫偶联物已在临床环境中实现了概念验证。在本文中，我们综述了前述细胞毒性平台的特点及其化学偶联方法。
