Uncovering therapeutic opportunities in the clinical development of antibody-drug conjugates

IntroductionAntibody-drug conjugates (ADCs) are a family of therapeutic agents that have demonstrated clinical activity in several indications.Material and methodsIn 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.ResultsWe 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.ConclusionsIn summary, our study opens the door for further evaluation of ADCs in several indications not explored before. & BULL; Most ongoing Antibody-drug conjugates (ADCs) have a classical structure, with a minority of them with specific formats & BULL; ADCs against TAAs of haematological malignancies are more specific than those for solid tumours.& BULL; Niche indications for ADCs included targets for CD71, PSMA, PTK7 or CD74, in breast, lung, stomach or colon cancer.& BULL; Some of these TAAs are essential genes like CD71, PSMA and PTK7 & BULL; This study opens the door for further evaluation of ADCs in non-explored indications.image

Automated summary

ADCs have shown clinical activity in various indications, with TATs for haematological malignancies being more specific than those for solid tumors. There are unexplored niche indications for ADCs in solid tumors, and some TATs are essential for the survival of tumor cells like CD71, PSMA, and PTK7.