The following article comes from Kaijie Life Sciences, author Kaijie

Kaijie Life Sciences.

QIAGEN is the world's leading supplier of sample preparation and analysis technology. Relying on its world-leading technology and expertise, the company continues to expand the market from sample preparation, analysis to data interpretation. In the research and testing process in the fields of academic research, applied testing, biomedicine and molecular diagnostics, more than 500,000 customers around the world have chosen QIAGEN.

抗体偶联药物(ADC)将靶向特异性抗原的单克隆抗体与细胞毒性小分子药物结合,可以选择性杀死目标肿瘤细胞。近年来,国内外ADC药物靶抗原主要集中在HER2、TROP2、EGFR等热门分子。 The selection of new target antigens usually requires consideration of their expression profile characteristics (tumor cells vs. normal cells), subcellular positioning, cellular endocytosis, etc., so as to minimize extra-tumor toxicity.

Figure 1. ADC drug action mechanism [1].

近年来,高通量测序技术积累了海量样本的组学数据信息,可以帮助研究者深入分析潜在靶抗原在特定肿瘤中的组学特征,助力新靶抗原的发现。然而,来自世界各地的研究数据通常分散在不同数据库,阻碍了研究者进行数据的整合和挖掘。 It is understood that the OmicSoft Lands database developed by QIAGEN Company is manually collected and organized to summarize data from TCGA、ATCC、GEO、CCLE、GTEx、HPA Other databases>766,218 samples including transcriptome, single cell expression profiles, and somatic mutations, and 1,000 Various sample meta information. In addition, the Inauthenticity Pathway Analysis (IPA) developed by QIAGEN The database is based on published literature and summarizes 13.1 million pieces of biological evidence related to classic pathways, biological functions and diseases. Based on OmicSoft And IPA high-quality knowledge base, which can quickly query the expression profile, mutation information, subcellular localization, and endocytosis regulation mechanism of target antigens in specific tumors.

Query target antigen expression profile

2023年Seagen公司发表在Molecular Cancer Therapeutics的文章,研究了针对黑素铁转蛋白CD228抗原的ADC药物抗肿瘤活性 [2] 。该研究中The author used OmicSoft Lands to analyze the impact of CD228 on TCGA Expression levels in different types of tumors and different subtypes of breast cancer, and the correlation between expression spectrum data and mass spectrum data. 进一步的IHC实验结果与TCGA转录组数据一致,表明CD228在正常组织中低表达,在多种肿瘤中高表达。

Figure 2. A. Expression of CD228 in different types of TCGA tumors;B. Expression of CD228 in different subtypes of breast cancer;C. Correlation between CD228 transcriptome data and MS data.

2017年Novartis公司发表在Cancer Discovery杂志的文章,表明CDH6在卵巢癌和肾脏癌中高表达,并展示了结合药效机理学和毒理学的综合药理学策略如何为优化治疗方法提供丰富的数据集 [3] 。该研究中,The author analyzed the expression distribution of CDH6 in GTEx normal tissues and TCGA tumor tissues through OmicSoft Lands. 进一步通过IHC方法评估了临床原发肾癌和卵巢癌样本中CDH6蛋白表达量。

Figure 3. Expression distribution of CDH6 in GTEx normal tissues and TCGA tumor tissues.

Constructing a regulatory network for cellular endocytosis

ADC药物内吞途径和效率,直接影响了药物的设计和治疗效果 [4] 。IPA has included molecules and regulatory networks associated with four common endocytosis pathways ,包括网格蛋白介导的内吞作用 (Clathrin-Mediated

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