Nieto-Jiménez Cristina, Sanvicente Adrián, Díaz-Tejeiro Cristina, Moreno Víctor, Lopez de Sá Alfonso, Calvo Emiliano, Martínez-López Joaquín, Pérez-Segura Pedro, Ocaña Alberto
Experimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC) Instituto de investigación sanitaria San Carlos (IdISSC), Madrid, Spain.
Facultad Ciencias Químicas, Universidad Complutense, Madrid, Spain.
Clin Transl Med. 2023 Sep;13(9):e1329. doi: 10.1002/ctm2.1329.
Antibody-drug conjugates (ADCs) are a family of therapeutic agents that have demonstrated clinical activity in several indications.
In this article, we performed a deep analysis of their clinical landscape matched with public genomic human datasets from tumour antigen targets (TATs), to identify empty areas for clinical development.
We observed that TATs used in haematological malignancies were more specific than the ones developed in solid cancers. Those included CD19, CD22, CD30, CD33 and CD79b. In solid tumours, we identified TATs, with approved ADCs, widely expressed in non-explored niche indications like Enfortumab vedotin (anti-Nectin4) in lung or cervical cancer; Tisotumab vedotin (anti-TF) in glioblastoma or pancreatic cancer; and Sacituzumab govitecan (anti-TROP2) in pancreatic, gastric, thyroid or endometrial cancer, among others. Similarly, niche indications for ADCs in clinical development included targets for CD71, PSMA, PTK7 or CD74, in tumours like breast, lung, stomach or colon. Some of these TATs were essential for the survival of tumour cells like CD71, PSMA and PTK7.
In summary, our study opens the door for further evaluation of ADCs in several indications not explored before.
抗体药物偶联物（ADCs）是一类治疗药物，已在多种适应症中显示出临床活性。
在本文中，我们对其临床情况与来自肿瘤抗原靶点（TATs）的公共基因组人类数据集进行了深入分析，以确定临床开发的空白领域。
我们观察到，血液系统恶性肿瘤中使用的TATs比实体癌中开发的TATs更具特异性。这些包括CD19、CD22、CD30、CD33和CD79b。在实体瘤中，我们确定了一些已获批ADC药物的TATs，它们在未被充分探索的特定适应症中广泛表达，如恩杂鲁胺（抗Nectin4）用于肺癌或宫颈癌；替索单抗（抗TF）用于胶质母细胞瘤或胰腺癌；以及戈沙妥珠单抗（抗TROP2）用于胰腺癌、胃癌、甲状腺癌或子宫内膜癌等。同样，处于临床开发阶段的ADC药物的特定适应症还包括CD71、PSMA、PTK7或CD74等靶点，用于乳腺癌、肺癌、胃癌或结肠癌等肿瘤。其中一些TATs对肿瘤细胞的存活至关重要，如CD71、PSMA和PTK7。
总之，我们的研究为进一步评估ADC药物在以前未被探索的多种适应症中的应用打开了大门。
