Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model
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 capac...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05899-w |
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| author | Shao Duan Chao Li Feng Yan Yifei Xia Shuaiming Shao Weiyu Chen Zunyu Xiao Gongping Xu |
| author_facet | Shao Duan Chao Li Feng Yan Yifei Xia Shuaiming Shao Weiyu Chen Zunyu Xiao Gongping Xu |
| author_sort | Shao Duan |
| collection | DOAJ |
| description | 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 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 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. |
| format | Article |
| id | doaj-art-04ff0dbbd99d49f08b202945c35a5217 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-04ff0dbbd99d49f08b202945c35a52172025-02-09T12:52:28ZengBMCJournal of Translational Medicine1479-58762025-02-0123111610.1186/s12967-024-05899-wNon-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse modelShao Duan0Chao Li1Feng Yan2Yifei Xia3Shuaiming Shao4Weiyu Chen5Zunyu Xiao6Gongping Xu7Department of Orthopedics, the Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, the People’s Hospital of Suzhou New DistricDepartment of Orthopedics, the Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, the People’s Hospital of Suzhou New DistricDepartment of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, Zhejiang University School of MedicineDepartment of Nuclear Medicine, The First Affiliated Hospital of Ningbo UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Harbin Medical UniversityAbstract 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 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 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.https://doi.org/10.1186/s12967-024-05899-wICOSNIRF imagingRheumatoid arthritisHumanized modelActivated T cell |
| spellingShingle | Shao Duan Chao Li Feng Yan Yifei Xia Shuaiming Shao Weiyu Chen Zunyu Xiao Gongping Xu Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model Journal of Translational Medicine ICOS NIRF imaging Rheumatoid arthritis Humanized model Activated T cell |
| title | Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model |
| title_full | Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model |
| title_fullStr | Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model |
| title_full_unstemmed | Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model |
| title_short | Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model |
| title_sort | non invasive imaging with icos targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model |
| topic | ICOS NIRF imaging Rheumatoid arthritis Humanized model Activated T cell |
| url | https://doi.org/10.1186/s12967-024-05899-w |
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