The Science
Overcoming barriers, the next step in effective engineered cell therapies in solid tumor therapy
Cellular immunotherapy faces severe limitations in advanced solid tumors because engineered cells reaching the tumor site confront a highly immunosuppressive microenvironment. This immunosuppressive activity is promoted in large extend by TGFβ production. This pleiotropic growth factor recruits immunosuppressive cells such as Tregs and myeloid cells while decreasing NK and CD8 T cell function. Thus, most engineered cellular therapies are effectively stopped in their tracks.
Our Chimeric TGFB Signaling Receptor (CTSR) platform addresses the immunosuppressive barrier of
solid tumors by reversing the effects of TGFβ on engineered cells and alleviating TGFβ effects on other immune cells.
Reversing the effects of a suppressive tumor microenvironment greatly improves the effects of Chimeric Antigen Receptor (CAR) cell therapies against solid tumors
Graphical representation of the Chimeric TGFB Signaling Receptor (CTSR) module
Current cellular immunotherapies work by binding to and killing tumor cells that overexpress “tumor-specific” antigens. The challenge with this approach is that most of these antigens are not truly tumor-specific and are also expressed on normal cells. Thus, most cancer therapies result in on-target, off-tumor killing of normal cells, ultimately leading to unacceptable toxicities.
We invented a precision-targeting cellular system – the Tmod™ mechanism – that incorporates two receptors, an activator and a blocker to aim the powerful armaments of immune cells directly at tumors.
The activator recognizes antigens on tumor cells that trigger their killing, while the blocker recognizes antigens on normal cells that protect them from destruction.
Exploiting the loss of genes in tumor cells, known as loss of heterozygosity (LOH), provides an opportunity to unequivocally differentiate tumors from normal tissues.
The CTSR platform is robustly different from other cell therapy systems.
Our CTSR platform is a completely independent genetic module, fully compatible with all current and future CAR technologies. It can be integrated seamlessly to any manufacturing process to produce tumor specific CARs which are resistant to the tumor microenvironment.
