Development and characterization of novel anti GD2 target modules for retargeting of Universal CAR T cells toward GD2 expressing tumors

Although chimeric antigen receptor (CAR) engineered T cells demonstrated promising therapeutic effect against cancer, they are still associated with adverse side effects which could be life threatening in some cases. Therefore, in our group we have developed a switchable universal CAR T cell platform “UniCAR”, which can be repeatedly switched on and off. This system consists of CAR T cells that cannot bind tumor antigens directly but instead they are redirected with a target module (TM). Such TMs are mainly composed of an epitope on one side, which is recognized by the UniCAR T cells, and on the other side a tumor antigen-binding domain. Once the TM is eliminated, the UniCAR T cells are no more activated. Disialoganglioside GD2 was shown previously to be a very promising target for several tumors such as neuroblastoma and Ewing’s sarcomas. Therefore, anti-GD2 TMs were developed and evaluated regarding their functionality. They were shown to be functional in activating the UniCARs to secrete important pro-inflammatory cytokines and to kill GD2+ tumor cells both in vivo and in vitro. To further characterize the anti-GD2 TM with PET imaging, it was labeled with radioactive Cu64 . The TM showed a specific enrichment at the site of the GD2+ growing tumor, and it was mainly eliminated through the kidneys within half an hour due to its small size. Such short half-life, provides the UniCAR system with the fast safety switch in case any complications occurred in patients treated with the UniCAR T cells.