Development of radio cell theranostics in oncology

This research project aims to develop a modular radio-cell theranostic platform that integrates molecular imaging with adoptive cell immunotherapy. We engineered viral vectors to endow human effector cells with dual functions: non-invasive in vivo tracking and antigen-driven recruitment of therapeutic radionuclides. Two inducible circuits were implemented: NFAT-responsive transcription and SynNotch-GAL4, and an EF1a-driven constitutive expression; both inducible and constitutive systems focused on the human sodium iodide symporter (hNIS) and avidin/monodin (biotin-binding) receptors. The project goal was to enable imaging of activated cells and localised radiation delivery through radionuclide uptake. Lentiviral and retroviral backbones were designed to express hNIS, CD8TM-avidin, or CD8TM-monodin genes and those constructs were validated in Jurkat and primary Pan-T cells. Constitutive systems established feasibility across cell contexts, revealing cell-type-dependent receptor display (e.g., higher monodin surface signal in Jurkat versus relatively better avidin detection in primary T cells). In contrast, the inducible NFAT and SynNotch architectures provided stimulus-dependent control but showed suboptimal induction and context-dependent leakiness in Jurkat cells, highlighting the need to refine promoter/enhancer design and chromatin accessibility to maximise on/off ratios. Collectively, the data deliver a proof-of-concept for dual-function immune cells capable of diagnostic imaging and targeted radiotherapy, while delineating clear engineering priorities, stronger inducible promoters, signal amplification, AND-gate logic, and safety switches, to progress toward clinically viable, programmable cell therapies.