Engineering monocytes and macrophages for therapeutic control

Engineered monocytes and macrophages are emerging as therapeutic platforms for eliminating pathological targets, remodeling diseased tissues, and coordinating local immune responses. Early clinical studies support their feasibility, but target recognition alone does not ensure sustained function after tissue entry. Recent advances in myeloid-adapted receptors, context-responsive circuits, checkpoint and metabolic engineering, in vivo mRNA delivery, and stem-cell-derived platforms have expanded the strategies available to improve tissue tracking, control cellular plasticity, and sustain effector capacity. Previous reviews have commonly organized the field by disease, target, or platform. Here, we examine engineered monocyte and macrophage therapies as integrated pharmacological systems structured across four coupled layers-sensing, signal integration, actuation, and delivery-and discuss how their coordination determines tissue exposure, functional durability, and pharmacodynamic readouts across therapeutic settings.