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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)520-528
Number of pages9
JournalMolecular Therapy - Nucleic Acids
Volume8
DOIs
Publication statusPublished - Sep 15 2017

Keywords

  • aptamer
  • cancer
  • CTLA-4
  • immunotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Huang, B. T., Lai, W. Y., Chang, Y. C., Wang, J. W., Yeh, S. D., Lin, E. P. Y., & Yang, P. C. (2017). A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect. Molecular Therapy - Nucleic Acids, 8, 520-528. https://doi.org/10.1016/j.omtn.2017.08.006