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

Abstract

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.

• Authors: Xuejun Wen, Xueyuan Zeng, Xingxing Cheng, Xinying Zeng, Jia Liu, Yiren Zhang, Yesen Li, Haojun Chen, Jinxiong Huang, Zhide Guo, Xiaoyuan Chen, Xianzhong Zhang
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 19 Issue 10 Pg. 3612-3622 (10 03 2022) ISSN: 1543-8392 [Electronic] United States
• PMID: 35652897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Immune Checkpoint Inhibitors
• Immunologic Factors
• Iodine Radioisotopes
• Iodine-131
• Ligands
• Programmed Cell Death 1 Receptor
• Receptors, Death Domain

Topics

• Animals
• Antibodies
• Cell Line, Tumor
• Humans
• Immune Checkpoint Inhibitors
• Immunologic Factors
• Immunotherapy (methods)
• Iodine Radioisotopes (therapeutic use)
• Ligands
• Mice
• Neoplasms (therapy)
• Programmed Cell Death 1 Receptor
• Receptors, Death Domain