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Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice.
Acta Pharmaceutica Sinica B ( IF 14.5 ) Pub Date : 2020-02-19 , DOI: 10.1016/j.apsb.2020.02.004
Haifeng Huang 1, 2 , Hua Zhu 3 , Quan Xie 1 , Xiaobin Tian 1 , Xianteng Yang 1, 2 , Fan Feng 4 , Qiyu Jiang 4 , Xinan Sheng 5 , Zhi Yang 3
Affiliation  

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.



中文翻译:

在人源化小鼠中使用肉瘤细胞同种移植评估hPD1免疫PET成像的124I-JS001。

JS001(toripalimab)是一种人源化IgG单克隆抗体,可强烈抑制程序性细胞死亡蛋白1(PD1)。在这项研究中,我们使用了不同的碘同种型(nat / 124/125 I)标记JS001探针,以靶向人PD1(hPD1)抗原。在体外nat I-JS001的半数最大有效浓度(EC 50)值与JS001没有显着差异。孵育2小时后,活化的T细胞对125 I-JS001的吸收比未活化的T细胞高5.63倍。植物血凝素(PHA)刺激后125 I-JS001与不同谱系的T细胞的结合亲和力达到4.26 nmol / L。人源化PD1验证具有小鼠肉瘤S180细胞肿瘤的C57BL / 6小鼠可用于免疫正电子发射断层扫描(immuno-PET)成像。病理染色用于评估PD1在肿瘤组织中的表达。同源124-人IgG(124-的hIgG)基团或封端基团被用作对照组。Immuno-PET成像显示在不同时间点124 I-JS001组肿瘤区域的摄取明显高于人源化PD1中的阻断组或124 I-hIgG组的摄取鼠标模型。综上所述,这些结果表明,这种放射性示踪剂具有用于PD1阳性肿瘤的无创监测和指导肿瘤特异性个性化免疫治疗的潜力。

更新日期:2020-02-19
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