Kurzfassung

Chimeric antigen receptors (CAR)-engineered T cells have demonstrated remarkable efficacy in patients with B-cell malignancies. Yet, serious adverse events (e.g. cytokine release syndrome or fatal outcome) were frequently observed. NK cells can enhance T-cell activation without production of cytokines linked to adverse reactions. This translational immunotherapy project aims to combine NK cells as effector cells with universal epitope-specific CAR (UniCAR) with tunable activity. The UniCAR is...Chimeric antigen receptors (CAR)-engineered T cells have demonstrated remarkable efficacy in patients with B-cell malignancies. Yet, serious adverse events (e.g. cytokine release syndrome or fatal outcome) were frequently observed. NK cells can enhance T-cell activation without production of cytokines linked to adverse reactions. This translational immunotherapy project aims to combine NK cells as effector cells with universal epitope-specific CAR (UniCAR) with tunable activity. The UniCAR is only activated upon cross-linking through a soluble tumor-targeting module carrying the UniCAR binding epitope, thereby achieving highest tumor specificity. Previous work from the contributing DKTK partner sites has demonstrated the versatility of this approach in T cells, and showed that it is feasible to derive CAR-engineered, established human NK cells as an off-the-shelf cellular therapeutic. Focusing on advanced melanoma, we will investigate the antitumor activity of UniCAR NK cells in clinically relevant models. Recombinant targeting modules will be based on antibodies and soluble single-chain fragments of TCR specific for melanoma antigens. Promising combinations of UniCAR NK cells and distinct targeting molecules will be identified for subsequent translation into a phase clinical study.

The location Mainz is funded with an amount of 144.000 €.» weiterlesen» einklappen