Figure 1.

Retargeting of UniCAR T cells with the novel PET tracer-based PSMA PLT-TM. (a) In previous studies, we showed that UniCAR T cells can be retargeted to tumor cells via single-chain fragment variable (scFv)-based target modules (TMs). As schematically shown such scFv-based TMs represent a fusion molecule consisting of the respective scFv and the UniCAR epitope (E5B9). Thus, UniCAR T cells can form an immune complex with the TM, which allows the UniCAR T cell to recognize a specific target on the surface of the tumor cells. (b) As the development of a scFv-based TM for a clinical application is time-consuming and cost-extensive, we wanted to learn whether or not functional TMs can also be constructed from low-molecular-weight molecules: E.g. based on the PSMA-specific ligand PSMA-HBED-CC (PSMA-11 analogue). In order to transform this tracer in a potential TM, we fused the E5B9 epitope during chemical synthesis with PSMA-HBED-CC (see also Figure 2). The resulting compound PSMA peptide/ligand tracer TM (PSMA PLT-TM) cannot only be used for PSMA-PET imaging but also for retargeting of UniCAR T cells to PSMA-positive tumor cells.