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

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...

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Main Authors: Haifeng Huang (Author), Hua Zhu (Author), Quan Xie (Author), Xiaobin Tian (Author), Xianteng Yang (Author), Fan Feng (Author), Qiyu Jiang (Author), Xinan Sheng (Author), Zhi Yang (Author)
Format: Book
Published: Elsevier, 2020-07-01T00:00:00Z.
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100 1 0 |a Haifeng Huang  |e author 
700 1 0 |a Hua Zhu  |e author 
700 1 0 |a Quan Xie  |e author 
700 1 0 |a Xiaobin Tian  |e author 
700 1 0 |a Xianteng Yang  |e author 
700 1 0 |a Fan Feng  |e author 
700 1 0 |a Qiyu Jiang  |e author 
700 1 0 |a Xinan Sheng  |e author 
700 1 0 |a Zhi Yang  |e author 
245 0 0 |a Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice 
260 |b Elsevier,   |c 2020-07-01T00:00:00Z. 
500 |a 2211-3835 
500 |a 10.1016/j.apsb.2020.02.004 
520 |a 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. 
546 |a EN 
690 |a Immunotherapy 
690 |a JS001 
690 |a Toripalimab 
690 |a Programmed cell death protein 1 
690 |a Immuno-PET imaging 
690 |a Iodine isotopes 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Acta Pharmaceutica Sinica B, Vol 10, Iss 7, Pp 1321-1330 (2020) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2211383519310214 
787 0 |n https://doaj.org/toc/2211-3835 
856 4 1 |u https://doaj.org/article/cfd2c39e4ddf4dce80d534baafe6310c  |z Connect to this object online.