Interrogating ligand-receptor interactions using highly sensitive cellular biosensors

被引:4
作者
Funk M.A. [1 ]
Leitner J. [1 ]
Gerner M.C. [2 ]
Hammerler J.M. [2 ]
Salzer B. [3 ,4 ]
Lehner M. [3 ,4 ]
Battin C. [1 ]
Gumpelmair S. [1 ]
Stiasny K. [5 ]
Grabmeier-Pfistershammer K. [6 ]
Steinberger P. [1 ]
机构
[1] Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division for Immune Receptors and T cell activation, Medical University of Vienna, Vienna
[2] Division of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna
[3] St. Anna Children’s Cancer Research Institute, Vienna
[4] Christian Doppler Laboratory for Next Generation CAR T Cells, Vienna
[5] Center for Virology, Medical University of Vienna, Vienna
[6] Department of Dermatology, Medical University of Vienna, Vienna
基金
美国国家卫生研究院; 奥地利科学基金会;
关键词
D O I
10.1038/s41467-023-43589-1
中图分类号
学科分类号
摘要
Interactions of membrane-resident proteins are important targets for therapeutic interventions but most methods to study them are either costly, laborious or fail to reflect the physiologic interaction of membrane resident proteins in trans. Here we describe highly sensitive cellular biosensors as a tool to study receptor-ligand pairs. They consist of fluorescent reporter cells that express chimeric receptors harboring ectodomains of cell surface molecules and intracellular signaling domains. We show that a broad range of molecules can be integrated into this platform and we demonstrate its applicability to highly relevant research areas, including the characterization of immune checkpoints and the probing of cells for the presence of receptors or ligands. The platform is suitable to evaluate the interactions of viral proteins with host receptors and to test for neutralization capability of drugs or biological samples. Our results indicate that cellular biosensors have broad utility as a tool to study protein-interactions. © 2023, The Author(s).
引用
收藏
相关论文
共 81 条
[21]  
Chen S., Et al., Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis, Front. Oncol., 11, (2021)
[22]  
Koblish H.K., Et al., Characterization of INCB086550: A Potent and Novel Small-Molecule PD-L1 Inhibitor, Cancer Discov., 12, pp. 1482-1499, (2022)
[23]  
Miller M.M., MACROCYCLIC INHIBITORS OF THE PD-1/PD-L1 AND CD80(B7-1)/PD-L1 PROTEIN/PROTEIN INTERACTIONS., (2014)
[24]  
Brautigam K., Et al., Inhibitors of PD-1/PD-L1 and ERK1/2 impede the proliferation of receptor positive and triple-negative breast cancer cell lines, J. Cancer Res. Clin. Oncol., 147, pp. 2923-2933, (2021)
[25]  
Zak K.M., Et al., Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1), Oncotarget, 7, pp. 30323-30335, (2016)
[26]  
Ashizawa T., Et al., Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse, Biomed. Res., 40, pp. 243-250, (2019)
[27]  
Nishimura C.D., Pulanco M.C., Cui W., Lu L., Zang X., PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies, Trends Mol. Med., 27, pp. 207-219, (2021)
[28]  
Sznol M., Et al., Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients (pts) with advanced cancer (CA.), J. Clin. Oncol., 26, (2008)
[29]  
Fisher T.S., Et al., Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity, Cancer Immunol. Immunother., 61, pp. 1721-1733, (2012)
[30]  
Chin S.M., Et al., Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab, Nat. Commun., 9, (2018)