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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