Harnessing the immune system to eradicate cancer has shown efficient results in recent years. A rapidly emerging immunotherapy approach is called adoptive cell transfer (ACT), in which collecting and using patients own engineered immune cells to treat their cancer. The most advance adoptive cell transfer with two approved products is called CAR-T. However, excess immune activation, mainly in the usage of CAR-T, holds the danger of an overt immune response leading to potentially severe side effects, autoimmunity or even death. Improved control of the expression of the engineered CAR-T is needed to reduce the risks of life-threatening “side-effect”.
We have developed a novel platform that regulates gene expression under the control of inflammation-induced promoters, together with a tet-response circuit. Several promoters were already tested in mouse and in human cells, demonstrating functional abilities to respond to major inflammatory cytokines and to their combinations.
Our research continues with examination of the potency and specificity in engineered immune cells ex-vivo and within the tumor microenvironment in-vivo. This novel platform can be applicable for ACT of most engineered immune cells.
Synthetic Promoters that control the expression of immune effector cells, such as CAR T-cells. To increase safety and reduce off-target effects, these promoters can focus immune activity specifically to tumor-microenvironment. Synthetic promoters are switched on by the induced immune-activation in inflammatory microenvironment, and includes multiple engineered elements to provide controlled precision intensity.
- Pronounced upregulation of expression in the induced state, compared with un-induced state.
- Optimal activation profile which may include minimal response to each single tumor-microenvironment signature factor and maximal response to the combination of two or more TME signature factors.
- Additional Tet-On safety mechanism are embedded within the platform.
- Readily applicable to any CAR-T or other adoptive-transfer engineered immune cells.
PCT patent application No. PCT/IL2019/050182 filed February 14, 2019