P2.03b-090 A CTLA-4 Antagonizing DNA Aptamer with Anti-Tumor Effect

The discovery of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade and its successful clinical translation has revolutionized the concept of cancer immunotherapy. Although immunecheckpoint-targeting antibody has shown impressive results in a diverse array of cancers, their cell-based manufacturing process influences production capacity and cause variation between batches. Aptamers are synthetic DNA or RNA oligonucleotides that encompass antibody-mimicking functions. With its chemically synthetic nature, aptamer can be produced in large scale with controllable batch variations and lower manufacturing cost. Here, we report the development of a CTLA-4 antagonizing DNA aptamer, termed aptCTLA-4, using the cell-based SELEX and next-generation sequencing. The aptCTLA-4 exhibits good binding affinity (dissociation constant, 11.8 nM). In vitro lymphocyte proliferation assays demonstrated that the aptCTLA-4 promotes T cell proliferation, and in vivo murine syngeneic tumor models further revealed its tumor-inhibitory effects. Our data suggest the translational potential of the aptCTLA-4 to be developed into a therapeutic aptamer.