首页|Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice

Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice

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JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1).In this study,we used a different iodine isotype (nat/124/125I) to label JS001 probes to target the human PD1 (hPD1) antigen.In vitro,the half maximal effective concentration (ECso) value of natI-JS001 did not significantly differ from that of JS001.The uptake of 125I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation.The binding affinity of 125I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L.Humanized PDI C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging.Pathological staining was used to assess the expression of PD1 in tumor tissues.The homologous 124I-human IgG (124I-hIgG) group or blocking group was used as a control group.Immuno-PET imaging showed that the uptake in the tumor area of the 124I-JS001 group at different time points was significantly higher than that of the blocking group or the 124I-hIgG group in the humanized PDI mouse model.Taken together,these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PDl-positive tumors.

ImmunotherapyJS001ToripalimabProgrammed cell death protein 1Immuno-PET imagingIodine isotopes

Haifeng Huang、Hua Zhu、Quan Xie、Xiaobin Tian、Xianteng Yang、Fan Feng、Qiyu Jiang、Xinan Sheng、Zhi Yang

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Guizhou University School of Medicine, Guizhou University, Guiyang 550025, China

Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

Research Center for Clinical and Translational Medicine, the 302nd Hospital of Chinese PLA, Beijing 100039,China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China

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We thank American Journal Experts (https://wwwajecom/) for the English language editing of this manuscriptThe current study was

2020

药学学报(英文版)

药学学报(英文版)

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年,卷(期)：2020.10(7)
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