Chemically induced dimerizers (CIDs) have emerged as one of the most powerful tools for artificially regulating signaling pathways in cells; however, currently available CID systems lack the properties desired for use in regulating cellular therapies. Here, we report the development of human antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule–protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. We demonstrate this concept by generating three antibodies that are highly selective for the BCL-xL–ABT-737 complex compared to BCL-xL alone. We show the potential of AbCIDs for application in regulating human cell therapies by using them to induce CRISPRa-mediated gene expression and to regulate CAR T-cell activation. We believe that the AbCIDs generated in this study will find application in regulating cell therapies and that the general method of AbCID development may lead to the creation of many new and orthogonal CIDs.

化学诱导的二聚体（CID）已成为人工调节细胞信号通路的最强大工具之一。然而，当前可用的CID系统缺乏用于调节细胞疗法所需的性质。在这里，我们通过选择识别结合的小分子产生的化学表位的合成抗体，从已知的小分子蛋白质复合物中报告了基于人类抗体的化学诱导二聚体（AbCIDs）的发展。我们通过产生三种对BCL-xL–ABT-737复合物（与单独的BCL-xL相比）具有高度选择性的抗体来证明这一概念。我们通过使用AbCIDs诱导CRISPRa介导的基因表达并调节CAR T细胞活化来显示其在调控人类细胞治疗中的应用潜力。