Materials-enabled cellular immunotherapy: from manufacturing to in vivo control

Cellular immunotherapies have transformed cancer treatment, but broader clinical impact often remains limited by centralized viral-vector-dependent manufacturing, poor performance in solid tumors, and incomplete control over safety and in vivo behavior. This review provides a mechanism-centered narrative synthesis of materials-enabled cellular immunotherapy, organized across the therapeutic workflow from ex vivo engineering to in vivo execution and control. We examine non-viral platforms for ex vivo immune-cell engineering, including electroporation, device-based delivery, lipid nanoparticles, polymeric systems, transposon-based installation, and genome editing, emphasizing the shift from transfection efficiency to product-quality engineering. We then analyze four in vivo nanocarrier-enabled architectures—transient programming, targeting logic, durable programming, and post-infusion boosting—followed by cell–material hybrid strategies that improve trafficking, local support, metabolic fitness, and regional retention in solid tumors. Finally, we review materials-enabled control layers, including remote actuation, molecular gating, layered safety mechanisms, and real-time monitoring. Across these domains, a common conclusion emerges: the key translational challenge is not only potency, but predictability, including reproducible manufacturing, controllable persistence, repeat-dosing feasibility, and interpretable safety. Materials are therefore best understood not as auxiliary add-ons, but as an engineering framework that may help convert cell therapy into a more controllable and scalable class of biological medicines. This review is intended primarily for platform developers, translational researchers, and regulatory scientists, with the goal of clarifying how engineered materials are reshaping cell therapy from a powerful biological intervention into a controllable therapeutic system.