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Project

 

A new approach to cancer treatment is the chimeric antigen receptor (CAR) therapy, which shows promising results fighting tumors in clinical trials. It consists of autologous isolated T cells modified with a chimeric receptor based on the T-cell receptor combined with the recognition domain of an antibody. Upon reinjection, CAR T-cells exhibit cytotoxicity with high affinity towards cells displaying the antigen. However, clinical trials have shown that as tumor antigens are not solely expressed on tumor cells, but also on healthy tissues, grave off-target effects like the Graft-versus-Host-Disease may occur. In order to avoid such side-effects, we engineer CAR T-cell lines specifically activated by factors of the tumor microenvironment. Controlled by a genetic AND-gate system the T cells need two input signals in order to express CAR. This would allow highly localized cytotoxic activity of T cells and provide safer cell-based cancer immunotherapy especially for solid tumors.

 

To date, there is an increasing need for precise (and personalized) medicine for cancer treatment. Chimeric antigen receptor (CAR) T-cells are an innovative tool that has proven its effectiveness in clinical settings for tumor antigen specific gene therapies. CARs are engineered receptors that can be expressed on the surface of T cells to target virtually any tumor associated antigen, allowing cytotoxicity against tumor antigens of interest. However, clinical trial data have shown that expression of tumor surface antigens in healthy cells can lead to severe off-target effects. In order to avoid such side-effects, we engineer a CAR T-cell line that is specifically activated by different components of the tumor microenvironment to enhance the efficacy of CAR T-cell therapy. Controlled by a genetic AND-gate system the expression of CAR required two input signals, thus providing a safer cell-based cancer immunotherapy especially for solid tumors.