Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice
Haifeng Huang, Hua Zhu, Quan Xie, Xiaobin Tian, Xianteng Yang, Fan Feng, Qiyu Jiang, Xinan Sheng, Zhi Yang
Abstract
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.