A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

被引：45

作者：

Huang, Bo-Tsang ^{[1
]}

Lai, Wei-Yun ^{[1
]}

Chang, Yi-Chung ^{[1
]}

Wang, Jen-Wei ^{[1
]}

Yeh, Shauh-Der ^{[1
,2
]}

Lin, Emily Pei-Ying ^{[1
,3
,4
]}

Yang, Pan-Chyr ^{[1
,5
,6
]}

机构：

[1] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[2] Taipei Med Univ Hosp, Dept Urol, Taipei, Taiwan

[3] Natl Taiwan Univ Hosp, Dept Med Res, Natl Ctr Excellence Clin Trials, Taipei, Taiwan

[4] Natl Taiwan Univ Hosp, Dept Med Res, Res Ctr, Taipei, Taiwan

[5] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan

[6] Natl Taiwan Univ, Coll Med, Taipei, Taiwan

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2017年 / 8卷

关键词：

IN-VITRO SELECTION; BINDING APTAMER; RECEPTOR-BINDING; ANTIBODIES; MOLECULES;

D O I：

10.1016/j.omtn.2017.08.006

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：520 / 528

页数：9

共 57 条

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