A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

Bo-Tsang Huang; Wei-Yun Lai; Yi-Chung Chang; Jen-Wei Wang; Shauh-Der Yeh; Emily Pei-Ying Lin; Pan-Chyr Yang

doi:10.1016/j.omtn.2017.08.006

A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

Mol Ther Nucleic Acids. 2017 Sep 15:8:520-528. doi: 10.1016/j.omtn.2017.08.006. Epub 2017 Aug 15.

Authors

Bo-Tsang Huang¹, Wei-Yun Lai¹, Yi-Chung Chang¹, Jen-Wei Wang¹, Shauh-Der Yeh², Emily Pei-Ying Lin³, Pan-Chyr Yang⁴

Affiliations

¹ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
² Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan.
³ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; National Center of Excellence for Clinical Trials and Research Center, Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: pylin@ibms.sinica.edu.tw.
⁴ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: pcyang@ntu.edu.tw.

Abstract

The successful translation of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade has revolutionized the concept of cancer immunotherapy. Although monoclonal antibody therapeutics remain the mainstream in clinical practice, aptamers are synthetic oligonucleotides that encompass antibody-mimicking functions. Here, we report a novel high-affinity CTLA-4-antagonizing DNA aptamer (dissociation constant, 11.84 nM), aptCTLA-4, which was identified by cell-based SELEX and high-throughput sequencing. aptCTLA-4 is relatively stable in serum, promotes lymphocyte proliferation, and inhibits tumor growth in cell and animal models. Our study demonstrates the developmental pipeline of a functional CTLA-4-targeting aptamer and suggests a translational potential for aptCTLA-4.

Keywords: CTLA-4; aptamer; cancer; immunotherapy.