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

• Published in: iScience Vol. 26; no. 8; p. 107367
• Main Authors: Zhu, Zhenyu, Yang, Zeliang, Zhu, Chuanda, Hu, Zixi, Jiang, Zhongyu, Gong, Jingjing, Yuan, Yuyao, Chen, Xi, Jin, Yan, Yin, Yuxin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.08.2023; Elsevier
• Subjects: Cancer; Immunology; Pharmacology; Pharmacology; Immunology; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107367

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. [Display omitted] •IDO-APT specifically binds IDO1 and inhibits its enzyme activity•IDO-APT internalized into cells by conjugating with nanoparticles•IDO-APT suppresses tumor growth and enhances immune response Immunology; Pharmacology; Cancer