Restricting CAR expression to the tumor microenvironment

Harnessing the immune system to eradicate cancer is proving highly efficient in recent years. The ability of immune cells to identify and destruct cancerous cells within the body is suggesting superior potency; however, such great power also possesses a potential hazard. Specifically, the usage of engineered immune cells such as Chimeric-Antigen-Receptor T-cells (CAR-T), which are being approved by the FDA for various cancers rapidly, still face the danger of an overt immune response that risk patient’s life. I.e. the threat of on-target-off-tumor toxicity for CAR-treated solid cancers in which most currently studied CAR targets could have some expression by particular cells in normal tissues. Therefore, improved control of the expression of the engineered chimeric receptor is needed to reduce the risks of such life-threatening “side-effect”. We thus developed a novel platform for regulation of CAR gene expression under the control of synthetic promoters activated by signals that are prevalent in the tumor microenvironment. This platform can improve the various types of CAR-T cells, as well as other adoptive-transfer of engineered immune cells that will provide specific identification of their targets within the body.