Pfizer Worldwide Research and Development, Oncology Research Unit, 401 Middletown Road, Pearl River, NY, USA.
Nat Prod Rep. 2013 May;30(5):625-39. doi: 10.1039/c3np20113a.
The Antibody Drug Conjugate (ADC) is a therapeutic modality consisting of a monoclonal antibody attached to a cytotoxic, small-molecule payload. The antibody portion of the ADC serves as a transport vehicle that recognizes and binds to a protein antigen expressed in tumor tissues. The localized delivery and release of the payload within or near malignant cells allows for targeted delivery of a potent cytotoxic agent to diseased tissue, while reducing damage to antigen-negative, normal tissues. Recent years have witnessed an explosive increase in ADC-based therapies, due mainly to clinical reports of activity in both hematologic and epithelial cancers. Accompanying this upsurge in ADC development is a renewed interest in natural product cytotoxins, which are typically highly potent cell-killing agents, but suffer from poor drug-like properties and narrow safety margins when systemically administered as conventional chemotherapeutics. In this review, we discuss recent advances related to the construction of ADCs, the optimization of ADC safety and efficacy, and the increasingly pivotal roles of natural product payloads in the current and future landscape of ADC therapy.
抗体药物偶联物（ADC）是一种治疗方式，由与细胞毒性小分子有效载荷连接的单克隆抗体组成。ADC 的抗体部分作为运输载体，识别并结合在肿瘤组织中表达的蛋白质抗原。有效载荷在恶性细胞内或附近的局部递送和释放允许将有效的细胞毒性剂靶向递送至病变组织，同时减少对抗原阴性的正常组织的损伤。近年来，由于在血液系统和上皮性癌症中的临床活性报告，抗体药物偶联物治疗呈爆炸式增长。伴随着 ADC 开发的热潮，人们对天然产物细胞毒素重新产生了兴趣，天然产物细胞毒素通常是高效的细胞杀伤剂，但当作为常规化疗药物全身给药时，其具有较差的类药性和较窄的安全边际。在这篇综述中，我们讨论了与 ADC 构建、ADC 安全性和疗效的优化以及天然产物有效载荷在当前和未来 ADC 治疗领域中的日益关键作用相关的最新进展。
