Engineering immune cell engagers: From molecular constructs to biomaterial platforms

Immune cell engagers (ICEs) are emerging therapeutic platforms that redirect immune effector cells toward cancer cells by physically bridging immune-cell receptors with tumor-associated targets. This cell-bridging mechanism converts molecular recognition into localized immune activation, immune synapse formation, cytotoxic killing, or phagocytic clearance. Such contact-centered immune redirection complements immune checkpoint blockade, which can restore antitumor immunity but does not directly promote the physical immune cell-tumor cell contact required for productive effector functions. Building on this principle, advances in molecular and biomaterial engineering have expanded ICE design beyond conventional molecular formats, enabling programmable molecular bridges, engineered living cell surfaces, and material-scaffolded systems that coordinate tumor targeting, immune-cell recruitment, and functional modulation. In this review, we organized these approaches according to three levels of ICE engineering: (1) molecular ICEs such as engineered antibodies and aptamers, (2) living cell engagers based on cell surface engineering using molecular constructs or biomaterials and (3) nanoparticle platforms. Across these platforms, we discuss molecular architecture, tumor-targeting specificity, immune cell recruitment, and functional modulation as key factors governing direct immune-tumor cell interactions. By connecting diverse strategies through a common cell-engagement perspective, this review highlights how these approaches can provide functional and spatial advantages for next-generation cancer immunotherapy.