A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect.

Authors :: Huang BT
Lai WY
Chang YC
Wang JW
Yeh SD
Lin EP
Yang PC
Source :: Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2017 Sep 15; Vol. 8, pp. 520-528. Date of Electronic Publication: 2017 Aug 15.
Publication Year :: 2017
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.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)