PD-L1-Targeted Radionuclide Therapy Combined with αPD-L1 Antibody Immunotherapy Synergistically Improves the Antitumor Effect

• Published in: Molecular pharmaceutics 2022-10, Vol.19 (10), p.3612-3622
• Main Authors: Wen, Xuejun, Zeng, Xueyuan, Cheng, Xingxing, Zeng, Xinying, Liu, Jia, Zhang, Yiren, Li, Yesen, Chen, Haojun, Huang, Jinxiong, Guo, Zhide, Chen, Xiaoyuan, Zhang, Xianzhong
• Format: Article
• Language: English
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.2c00281

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 (131I-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 131I-αPD-L1. ImmunoSPECT imaging and biodistributions of 131I-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 131I-αPD-L1 revealed improved tumor control in murine tumor models. The combination of 11.1 MBq of 131I-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.