Qiagen’s scinetists in its subsidiary Cellectis’s lead by Dr Alexandre Juillerat have designed a new CAR architecture that contains an integrated microenvironment sensor. Their work was recently published in a scientific magazine “Scientific Reports”.
Low oxygen concentration is recognized as a hallmark of the microenvironment of certain solid tumors. The implementation of the novel oxygen sensitive CAR architecture empowers CAR T-cells with the possibility to auto-regulate (switch on or tune-up) their functions in low oxygen (hypoxic) environments.
With the primary purpose of implementing additional levels of safety to the CAR T-cell technologies, in particular to minimize “on-target / off-tumor” effects, this study demonstrated the possibility to use peculiarities of the tumor microenvironment to create self-decision making CAR T-cells with impaired functions at high oxygen concentration.
The results showed that this system also possessed the key feature to be prone to quickly return to its off state in the absence of the inducing signal (hypoxia), a characteristic that is of prime interest to protect healthy tissues distant from the tumor site. Beyond this first in vitro proof of concept, additional studies are expected to fully assess the therapeutic potential of this approach.