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
Affiliations
Zhenyu Zhu
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
Zeliang Yang
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
Chuanda Zhu
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
Zixi Hu
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
Zhongyu Jiang
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
Jingjing Gong
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
Yuyao Yuan
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
Xi Chen
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
Yan Jin
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
Yuxin Yin
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; Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, China; Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China; Corresponding author
Summary: 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.
