Near-infrared fluorescence-labeled anti-PD-L1-mAb for tumor imaging in human colorectal cancer xenografted mice
Near-infrared fluorescence-labeled anti-PD-L1-mAb for tumor imaging in human colorectal cancer xenografted mice
复制标题
近红外荧光标记的抗 PD-L1-mAb 用于人结直肠癌异种移植小鼠的肿瘤成像
DOI：
10.1002/jcb.28308
复制
发表时间：
2019
影响因子：
4
通讯作者：
Zhongqi Sun
中科院分区：
文献类型：
--
作者：
Mingyu Zhang;Huijie Jiang;Rongjun Zhang;Hao Jiang;Hailong Xu;Wenbin Pan;Xiaolin Gao;Zhongqi Sun
肿瘤中程序性死亡配体-1（PD-L1）的表达已被用作预测抗PD-L1免疫治疗反应的生物标志物。为了开发一种非侵入性成像技术来监测结直肠癌（CRC）中PD-L1表达的动态变化，我们用近红外（NIR）染料标记了抗PD-L1单克隆抗体，并通过进行光学成像来测试NIR-PD-L1-mAb探针监测CRC异种移植小鼠中PD-L1表达的能力。与通过流式细胞术和蛋白质印迹分析在体外三种CRC细胞系中PD-L1蛋白的表达水平一致，我们的体内成像显示携带SW 620 CRC细胞的小鼠中异种移植肿瘤的最高荧光信号，其次是来自SW 480和HCT 8细胞系的肿瘤。我们在注射NIR-PD-L1-mAb后120小时检测到肿瘤的最高荧光强度。在SW 620异种移植小鼠中，在肿瘤中观察到最高的荧光强度，其次是脾脏和肝脏。然而，在SW 480和HCT 8异种移植小鼠中，在脾脏中检测到最高的荧光信号，其次是肝脏和肿瘤。我们的研究结果表明，SW 620细胞表达更高水平的PD-L1，并且NIR-PD-L1-mAb与CRC细胞表面的PD-L1结合是特异性的。该技术是安全的，可以提供有关肿瘤PD-L1表达的有价值的信息，用于制定个性化靶向免疫治疗的治疗策略以及CRC患者的治疗反应。
The expression of programmed death ligand‐1 (PD‐L1) in tumor has been used as a biomarker to predict the anti‐PD‐L1 immunotherapy response. To develop a noninvasive imaging technique to monitor the dynamic changes in PD‐L1 expression in colorectal cancer (CRC), we labeled an anti‐PD‐L1 monoclonal antibody with near‐infrared (NIR) dye and tested the ability of the NIR‐PD‐L1‐mAb probe to monitor the PD‐L1 expression in CRC‐xenografted mice by performing optical imaging. Consistent with the expression levels of PD‐L1 protein in three CRC cell lines in vitro by flow cytometry and Western blot analyses, our in vivo imaging showed the highest fluorescence signal of the xenografted tumors in mice bearing SW620 CRC cells, followed by tumors derived from SW480 and HCT8 cell lines. We detected the highest fluorescent intensity of the tumor at 120 hours after injection of NIR‐PD‐L1‐mAb. The highest fluorescence intensity was seen in the tumor, followed by the spleen and the liver in SW620 xenografted mice. In SW480 and HCT8 xenografted mice, however, the highest fluorescent signals were detected in the spleen, followed by the liver and the tumor. Our findings indicate that SW620 cells express a higher level of PD‐L1, and the NIR‐PD‐L1‐mAb binding to PD‐L1 on the surface of CRC cells was specific. The technique was safe and could provide valuable information on PD‐L1 expression of the tumor for development of a therapeutic strategy of personized targeted immunotherapies as well as treatment response of patients with CRC.