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

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 journal › Article › peer-review

52 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 language	English
Pages (from-to)	520-528
Number of pages	9
Journal	Molecular Therapy Nucleic Acids
Volume	8
DOIs	https://doi.org/10.1016/j.omtn.2017.08.006
Publication status	Published - Sept 15 2017

Keywords

CTLA-4
aptamer
cancer
immunotherapy

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.omtn.2017.08.006

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title = "A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect",

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",

author = "Huang, {Bo Tsang} and Lai, {Wei Yun} and Chang, {Yi Chung} and Wang, {Jen Wei} and Yeh, {Shauh Der} and Lin, {Emily Pei Ying} and Yang, {Pan Chyr}",

note = "Funding Information: We dedicate this work to Dr. Konan Peck, a respected researcher in the fields of high-throughput biotechnology, biophysics, and cancer genomics. Shortly after initiating this project, Dr. Peck unfortunately succumbed to a rapidly progressing cancer. It is our fervent hope that the research platform established by Dr. Peck will result in the development of new diagnostic and therapeutic options that benefit cancer patients. We also thank the National Center for Genome Medicine for the technical and bioinformatics support. This project was supported by grants from the National Science Council ( NSC99-2320-B-001-012-MY3 and MOST104-2314-B-002-228-MY3 ). ",

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doi = "10.1016/j.omtn.2017.08.006",

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AU - Wang, Jen Wei

AU - Yeh, Shauh Der

AU - Lin, Emily Pei Ying

AU - Yang, Pan Chyr

N1 - Funding Information: We dedicate this work to Dr. Konan Peck, a respected researcher in the fields of high-throughput biotechnology, biophysics, and cancer genomics. Shortly after initiating this project, Dr. Peck unfortunately succumbed to a rapidly progressing cancer. It is our fervent hope that the research platform established by Dr. Peck will result in the development of new diagnostic and therapeutic options that benefit cancer patients. We also thank the National Center for Genome Medicine for the technical and bioinformatics support. This project was supported by grants from the National Science Council ( NSC99-2320-B-001-012-MY3 and MOST104-2314-B-002-228-MY3 ).

PY - 2017/9/15

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N2 - 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.

AB - 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.

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A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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