State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen 361102, China.
Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Mol Pharm. 2022 Oct 3;19(10):3612-3622. doi: 10.1021/acs.molpharmaceut.2c00281. Epub 2022 Jun 2.
Immune checkpoint blockers (ICBs) targeting programmed death receptor 1 (PD-1) ligand 1 (PD-L1) for immunotherapy have radically reformed oncology. It is of great significance to enhance the response rate of ICB in cancer patients. Here, a radioiodinated anti-PD-L1 antibody (I-αPD-L1) was developed for PD-L1-targeted single-photon emission computed tomography (SPECT) imaging and αPD-L1 immunotherapy. Flow cytometry and immunofluorescence staining were performed to identify PD-L1 upregulation in a time- and dose-dependent manner after being induced by I-αPD-L1. ImmunoSPECT imaging and biodistributions of I-αPD-L1 in CT26, MC38, 4T1, and B16F10 tumor models were conducted to visualize the high tumor uptake and low background signal. Compared to monotherapy alone, concurrent administration of αPD-L1 mAb and I-αPD-L1 revealed improved tumor control in murine tumor models. The combination of 11.1 MBq of I-αPD-L1 and 200 μg of αPD-L1 mAb resulted in significant tumor growth delay and prolonged survival. This radioligand synergized immunotherapy strategy holds great potential for cancer management.
免疫检查点抑制剂（ICBs）针对程序性死亡受体 1（PD-1）配体 1（PD-L1）进行免疫治疗，从根本上改变了肿瘤学。提高癌症患者 ICB 的反应率具有重要意义。在这里，开发了一种放射性碘标记的抗 PD-L1 抗体（I-αPD-L1），用于 PD-L1 靶向的单光子发射计算机断层扫描（SPECT）成像和αPD-L1 免疫治疗。流式细胞术和免疫荧光染色用于鉴定 I-αPD-L1 诱导后 PD-L1 的时间和剂量依赖性上调。在 CT26、MC38、4T1 和 B16F10 肿瘤模型中进行免疫 SPECT 成像和 I-αPD-L1 的生物分布，以可视化高肿瘤摄取和低背景信号。与单独的单药治疗相比，αPD-L1 mAb 和 I-αPD-L1 的同时给药显示出在小鼠肿瘤模型中改善的肿瘤控制。11.1 MBq 的 I-αPD-L1 和 200μg 的αPD-L1 mAb 的组合导致显著的肿瘤生长延迟和延长的生存。这种放射性配体协同免疫治疗策略在癌症管理方面具有巨大的潜力。
