Harnessing the Formation of Natural Killer–Tumor Cell Immunological Synapses for Enhanced Therapeutic Effect in Solid Tumors

Abstract The formation of an immunological synapse (IS) on recognition of a cancer cell is the main mechanism underlying the natural killer (NK)‐cell‐mediated killing of tumor cells. Herein, an integrative strategy for cancer therapy against solid tumors is reported, in which alterations in the cleft of IS, following the secretion of acidic granular content, are utilized as a trigger for the delivery of chemotherapeutic drugs. NK cells are decorated with the IS‐environment‐responsive micellar system to ensure the release of the payload when they attack cancer cells. Using this strategy, the immunological cytotoxic killing effect of NK cells against solid tumors is reinforced with the site‐specific diffusion of chemotherapeutic agents. Harnessing the intrinsic mechanism for the recognition of abnormal cells and the tumor‐homing effect of NK cells limit the adverse systemic effects of chemotherapeutic drugs. This approach may provide a pragmatic platform for the universal and effective utilization of IS formation.