Development of a DNA aptamer targeting IDO1 with anti-tumor effects

Zhenyu Zhu; Zeliang Yang; Chuanda Zhu; Zixi Hu; Zhongyu Jiang; Jingjing Gong; Yuyao Yuan; Xi Chen; Yan Jin; Yuxin Yin

doi:10.1016/j.isci.2023.107367

Development of a DNA aptamer targeting IDO1 with anti-tumor effects

iScience. 2023 Jul 13;26(8):107367. doi: 10.1016/j.isci.2023.107367. eCollection 2023 Aug 18.

Authors

Zhenyu Zhu¹, Zeliang Yang¹, Chuanda Zhu¹, Zixi Hu¹, Zhongyu Jiang¹, Jingjing Gong¹, Yuyao Yuan¹, Xi Chen¹, Yan Jin¹, Yuxin Yin^{1

2

3}

Affiliations

¹ Institute of Systems Biomedicine, Department of Pathology, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
² Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, China.
³ Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China.

Abstract

Immune checkpoint blockade has become an effective approach to reverse the immune tolerance of tumor cells. Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently upregulated in many types of cancers and contributes to the establishment of an immunosuppressive cancer microenvironment, which has been thought to be a potential target for cancer therapy. However, the development of IDO1 inhibitors for clinical application is still limited. Here, we isolated a DNA aptamer with a strong affinity and inhibitory activity against IDO1, designated as IDO-APT. By conjugating with nanoparticles, in situ injection of IDO-APT to CT26 tumor-bearing mice significantly suppresses the activity of regulatory T cells and promotes the function of CD8⁺ T cells, leading to tumor suppression and prolonged survival. Therefore, this functional IDO1-specific aptamer with potent anti-tumor effects may serve as a potential therapeutic strategy in cancer immunotherapy. Our data provide an alternative way to target IDO1 in addition to small molecule inhibitors.

Keywords: Cancer; Immunology; Pharmacology.