An Aptamer‐Functionalized DNA Circuit to Establish an Artificial Interaction between T Cells and Cancer Cells

Abstract Nongenetic strategies that enable control over the cell‐cell interaction network would be highly desired, particularly in T cell‐based cancer immunotherapy. In this work, we developed an aptamer‐functionalized DNA circuit to modulate the interaction between T cells and cancer cells. This DNA circuit was composed of recognition‐then‐triggering and aggregation‐then‐activation modules. Upon recognizing target cancer cells, the triggering strand was released to induce aggregation of immune receptors on the T cell surface, leading to an enhancement of T cell activity for effective cancer eradication. Our results demonstrated the feasibility of this DNA circuit for promoting target cancer cell‐directed stimulation of T cells, which, consequently, enhanced their killing effect on cancer cells. This DNA circuit, as a modular strategy to modulate intercellular interactions, could lead to a new paradigm for the development of nongenetic T cell‐based immunotherapy.