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.

抗体药物偶联物 (ADC) 代表了快速发展的肿瘤治疗类别，涵盖血液恶性肿瘤和实体癌的靶向治疗。ADC 研究的一个重要方面涉及识别最佳表面抗原，该抗原可以有效区分靶细胞和大多数哺乳动物细胞类型。在这里，我们设计了一种算法并编译了一个注释细胞膜蛋白的广泛数据集。该数据集源自全面的转录组、蛋白质组和基因组数据，涵盖 19 种实体癌以及正常组织。目的是发现潜在的治疗性表面抗原，以实现精确的 ADC 靶向。由此产生的靶标景观包括 165 种靶标和适应症组合，以及 75 种候选细胞表面蛋白。值得注意的是，其中 35 个候选药物具有适合 ADC 靶向的特性，并且之前在 ADC 研发中尚未报道过。此外，我们从 760 项临床试验中总共鉴定出了 159 种 ADC。其中，72 种 ADC 目前正在针对多种实体癌类型进行介入评估，针对 36 种独特抗原。我们使用这个综合注释数据集对它们在正常组织中的表达进行了分析，揭示了当前 ADC 靶点的各种概况。此外，我们强调靶抗原的生物学影响有可能增强其临床有效性。我们建议从多个方面考虑对靶抗原的成药性进行全面评估。这项研究代表了过去二十年对泛癌 ADC 靶点的彻底探索，强调了综合实体癌症靶点图谱拓宽 ADC 治疗范围的潜力。