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

Acta Pharmaceutica Sinica B

Xinan Sheng¹  Hua Zhu¹  Xiaobin Tian²  Haifeng Huang³  Qiyu Jiang³  Xianteng Yang³  Fan Feng³  Quan Xie⁴  Zhi Yang⁵ 

[1] Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, China;Institute, Beijing 100142, China;Guizhou University School of Medicine, Guizhou University, Guiyang 550025, China;;Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital &Research Center for Clinical and Translational Medicine, the 302nd Hospital of Chinese PLA, Beijing 100039, China;

关键词: Immunotherapy;    JS001;    Toripalimab;    Programmed cell death protein 1;    Immuno-PET imaging;    Iodine isotopes;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 (EC50) 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 PD1 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 PD1 mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.

【 授权许可】

Unknown