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在人源化小鼠中使用肉瘤细胞同种异体移植评估I-JS001用于hPD1免疫PET成像。

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

作者信息

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

机构信息

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

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

出版信息

Acta Pharm Sin B. 2020 Jul;10(7):1321-1330. doi: 10.1016/j.apsb.2020.02.004. Epub 2020 Feb 19.

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 (I) to label JS001 probes to target the human PD1 (hPD1) antigen. , the half maximal effective concentration (EC) value of I-JS001 did not significantly differ from that of JS001. The uptake of I-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 I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized 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 Ihuman IgG (IhIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the I-JS001 group at different time points was significantly higher than that of the blocking group or the I-hIgG group in the humanized 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.

摘要

JS001(托瑞帕利单抗)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)。在本研究中,我们使用不同的碘同位素(I)标记JS001探针,以靶向人PD1(hPD1)抗原。I-JS001的半数最大有效浓度(EC)值与JS001的该值无显著差异。孵育2小时后,活化T细胞对I-JS001的摄取比未活化T细胞高5.63倍。I-JS001对植物血凝素(PHA)刺激后不同谱系T细胞的结合亲和力达到4.26 nmol/L。对携带小鼠肉瘤S180细胞肿瘤的人源化C57BL/6小鼠进行免疫正电子发射断层扫描(immuno-PET)成像验证。采用病理染色评估肿瘤组织中PD1的表达。以同源人IgG(IhIgG)组或阻断组作为对照组。免疫PET成像显示,在人源化小鼠模型中,I-JS001组在不同时间点的肿瘤区域摄取显著高于阻断组或I-hIgG组。综上所述,这些结果表明这种放射性示踪剂在无创监测和指导PD1阳性肿瘤的肿瘤特异性个性化免疫治疗方面具有潜力。

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