Synthetic Receptors for Specific Cell Imaging and Signal Transduction
Zeynep-Büsra Tiren, Lotta Horrix, Doreen M. Floß, Sascha Malaczynski, Constantin Czekelius, Sebastian TemmeSpecific cell tracking or targeted modulation of cellular responses are often limited by the availability, specificity and effector functions of endogenous cell-surface receptors. Synthetic receptors with customizable functionality can overcome these limitations. Based on a qualitative survey of the literature, this narrative review describes the design, the functionality and the applications of nanobody-based synthetic receptor/ligand systems that employ either GFP/mCherry or the clinically approved humanized antibody Palivizumab as ligands. Depending on their molecular architecture, these systems can mediate cargo internalization for cell tracking or induce defined cellular responses through engineered interleukin, interferon, or Fas signaling pathways. We position these platforms within the broader field of synthetic receptors by discussing engineered GPCR- and Notch-based systems and briefly outline the development and clinical application of CAR T cells to illustrate the translational potential of synthetic receptor systems. Finally, we discuss the opportunities and limitations of GFP/mCherry- and Palivizumab-based systems, with particular emphasis on immunogenicity, in vivo applicability, manufacturability, scalability, and clinical translation. By linking modular receptor design to distinct functional outputs, this review highlights both the established value of GFP/mCherry- and Palivizumab-based synthetic receptor–ligand systems as experimental tools and their potential for future applications in molecular imaging and controlled signal transduction.