Team:Freiburg

Abstract

A new approach to cancer treatment is the chimeric antigen receptor (CAR) T cell 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.