Anti-TOSO CAR T Cells – Highly selective immunotherapeutic approach to CLL treatment

Cancer-immunotherapy is currently gaining interest thanks to novel genetic engineering technologies. The most promising approach is the chimeric antigen receptor (CAR) technique for redirecting hereby modified T cells against cancer-associated antigens. The herein presented CAR constitutes of a B cell-derived single chain antibody fragment (scFv) directed against TOSO. This ectodomain is fused with a co-stimulatory CD28 T cell activation domain, finally followed by a CD3ζ domain. The receptor is introduced into allogenic or autologous peripheral blood T cells by retroviral gene transfer.

Cell-based assays show high killing specificity of the anti-TOSO CAR T cells against CLL cells, whereas normal B cells remain intact. The discrimination is strongly improved in comparison to previously engineered anti-CD19 CAR T cells that are currently used in clinical studies.

The described anti-TOSO CAR T cells have a strongly improved selectivity of target cell killing. The reduction of adverse effects on normal cells provides a competitive advantage against all other CAR T cell approaches that are currently on the market.

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