Antitumor effect of PD-L1-targeting antagonistic aptamer-ASO delivery system with dual inhibitory function in immunotherapy

Published: 11 September 2023| Version 1 | DOI: 10.17632/t5cz9d59w5.1
Fatao Luo, Gang Yang, Xia Bai, Deyu Yuan, Ling Li, Diyue Wang, Xiaoxiang Lu, Yuchun Wang, Yiran Cheng, Xu Song, Yongyun Zhao


Checkpoint inhibitor antibody therapy by blocking the interaction of surface programmed death-ligand 1(PD-L1) and programmed cell death protein 1(PD-1) has promising advantages in cancer immunotherapy. However, the response of many patients remains unsatisfactorily, suspected to be relevant to PD-L1 located in other cellular compartments and antibodies do not have access to the intracellular compartments. Herein, we identify a PD-L1-targeting DNA aptamer (PA9-1) with dual roles, including an antagonist and a delivery agent dependent on PD-L1 internalization. And we design the PD-L1-targeting antagonistic aptamer-ASO delivery system (PA9-1-ASO), with synergistic inhibitory PD-L1 activity involving the combination of blockade and silencing mechanisms. This chimera not only blocks PD-L1/PD-1, but also achieves targeted delivery of the conjugated ASO to reduce both surface PD-L1 and total PD-L1 expression. Compared with the single blockade, this chimera with the dual inhibitory function synergistically inhibits PD-L1 to amplify immunotherapeutic efficacy, providing a promising synergistic strategy for immunotherapy.



Sichuan University


Aptamer, Immunotherapy, Antagonist, Oligonucleotide Delivery


Sichuan Province Science and Technology Support Program


Chengdu Municipal Science and Technology Program


Fundamental Research Funds for the Central Universities