Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model

作者：Shao Duan, Chao Li, Feng Yan, Yifei Xia, Shuai Shao, Weiyu Chen, Zunyu Xiao, Gongping Xu · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-024-05899-w · 被引用次数：3 · 研究领域：Rheumatoid Arthritis Research and Therapies、Advanced Biosensing Techniques and Applications、Systemic Lupus Erythematosus Research

Activated T cells play a pivotal role in rheumatoid arthritis (RA) pathogenesis, and imaging of activated T cells may provide a non-invasive tool for RA detection. Here, we first developed an optical probe targeting human inducible T cell co-stimulator (ICOS) and tested its capacity in RA diagnosis by capturing ICOS+ activated T cells in vivo in a humanized mouse model. The humanized arthritis model, Human peripheral blood mononuclear cells- adjuvant induced arthritis (HuPBMC-AIA) was established, and flow cytometry and immunofluorescence were employed to determine ICOS expression in huPBMC-AIA model. Anti-human ICOS monoclonal antibody (mAb) was conjugated to Cy7 via NHS ester amine reaction. A cell uptake study was used to confirm the specificity of Cy7-ICOS mAb to activated T cells. 4-view near-infrared fluorescence (NIRF) imaging study was performed to test Cy7-ICOS mAb in detecting RA in vivo. ICOS was confirmed as an indicator of RA pathogenesis via RNA-seq, flow cytometry and immunofluorescence data. An in-vitro cellular uptake study validated the specificity of Cy7-ICOS mAb to activated T cells. Cy7-ICOS mAb could detect ICOS+ activated T cells in vivo through 4-view NIRF imaging. The receiver operating characteristic (ROC) curve created based on NIRF imaging quantification could distinguish the huPBMC-AIA group from the control group at all time points imaged. In this study, we first developed an optical imaging probe targeting human ICOS, Cy7-ICOS mAb. The 4-view NI...