文章：

实体瘤中抗体-药物偶联物的目标图谱

The target atlas for antibody-drug conjugates across solid cancers 

原文发布日期：2023-12-21 

英文摘要：

Antibody-Drug Conjugates (ADCs) represent a rapidly advancing category of oncology therapeutics, spanning the targeted therapy for both hematologic malignancies and solid cancers. A crucial aspect of ADC research involves the identification of optimal surface antigens that can effectively differentiate target cells from most mammalian cell types. Herein, we have devised an algorithm and compiled an extensive dataset annotating cell membrane proteins. This dataset is derived from comprehensive transcriptomic, proteomic, and genomic data encompassing 19 types of solid cancer as well as normal tissues. The aim is to uncover potential therapeutic surface antigens for precise ADC targeting. The resulting target landscape comprises 165 combinations of targets and indications, along with 75 candidates of cell surface proteins. Notably, 35 of these candidates possess characteristics suitable for ADC targeting, and have not been previously reported in ADC research and development. Additionally, we have identified a total of 159 ADCs from a pool of 760 clinical trials. Of these, 72 ADCs are presently undergoing interventional evaluation for a variety of solid cancer types, targeting 36 unique antigens. We conducted an analysis of their expression in normal tissues using this comprehensive annotation dataset, revealing a diverse range of profiles for the current ADC targets. Moreover, we emphasize that the biological impacts of target antigens have the potential to enhance their clinical effectiveness. We propose a comprehensive assessment of the drugability of target antigens, considering multiple facets. This study represents a thorough exploration of pan-cancer ADC targets over the past two decades, underscoring the potential of a comprehensive solid cancer target atlas to broaden the scope of ADC therapies. 

摘要翻译： 

抗体药物偶联物（ADCs）是一类快速发展的肿瘤治疗药物，涵盖血液系统恶性肿瘤和实体瘤的靶向治疗。ADC研究的关键在于鉴定能够有效区分靶细胞与大多数哺乳动物细胞类型的最佳表面抗原。本研究设计了一种算法并构建了一个广泛的数据集，用于注释细胞膜蛋白。该数据集源自涵盖19种实体癌及正常组织的转录组、蛋白质组和基因组数据，旨在发现可用于ADC精准靶向的治疗性表面抗原。最终获得的靶点图谱包含165个靶点与适应症组合以及75个细胞表面蛋白候选物，其中35个候选物具有适合ADC靶向的特性，且此前未在ADC研发中被报道。此外，我们从760项临床试验中共识别出159种ADCs，其中72种ADC目前正针对多种实体癌类型进行介入性评估，靶向36种独特抗原。我们利用该综合注释数据集分析了这些靶点在正常组织中的表达情况，揭示了当前ADC靶点表达谱的多样性。此外，我们强调靶抗原的生物学效应可能增强其临床有效性，并提出应从多维度综合评估靶抗原的成药性。这项研究对过去二十年的泛癌ADC靶点进行了全面探索，证明了实体癌靶点全景图谱在拓展ADC治疗范围方面的潜力。

原文链接：

The target atlas for antibody-drug conjugates across solid cancers