NON-INVASIVE IMAGING WITH ICOS-TARGETING MONOCLONAL ANTIBODY FOR PRECLINICAL DIAGNOSIS OF RHEUMATOID ARTHRITIS IN A HUMANIZED MOUSE MODEL

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

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

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Abstract Background 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.Methods 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 Dry Mops 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.Findings ICOS was Speed Sensor Assemly 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.Conclusion In this study, we first developed an optical imaging probe targeting human ICOS, Cy7-ICOS mAb.The 4-view NIRF imaging with Cy7-ICOS mAb could detect pathogenic ICOS+ activated T cells with high sensitivity and specificity in vivo, which indicated the great potential of this imaging probe in RA early diagnosis.

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