A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect
Journal
Molecular Therapy - Nucleic Acids
Journal Volume
8
Pages
520-528
Date Issued
2017
Author(s)
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. ? 2017 The Author(s)
Subjects
aptamer; cancer; CTLA-4; immunotherapy
SDGs
Other Subjects
antineoplastic agent; aptamer; CTLA 4 antagonizing DNA aptamer; cytotoxic T lymphocyte antigen 4; DNA; unclassified drug; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; Article; binding affinity; cancer inhibition; controlled study; cytotoxic T lymphocyte; dissociation constant; drug dose escalation; drug protein binding; high throughput sequencing; human; in vitro study; in vivo study; Lewis carcinoma; lymphocyte proliferation; mouse; nonhuman; priority journal; systematic evolution of ligands by exponential enrichment aptamer technique; tumor associated leukocyte; tumor microenvironment
Publisher
Elsevier Inc
Type
journal article