Date: 2017-01-23
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Scientific Reports
Company: Cellectis (France)
Product: CAR T-cell therapy
Action
mechanism: cell therapy/immunotherapy product/gene therapy.
Disease:
Therapeutic area:
Country:
Trial details:
Latest
news: * On January 23, 2017, Cellectis announced the publication of a study in Scientific Reports, a Nature Publishing Group journal, describing a novel approach to a CAR design with an integrated environmental signal utilizing oxygen concentration to manipulate the CAR T-cell response.
In this report, Alexandre Juillerat, Ph.D. and his collaborators from the Cellectis innovation team designed a new CAR architecture that contains an integrated microenvironment sensor. 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 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.
(An oxygen sensitive self-decision making engineered CAR T-cell. Alexandre Juillerat, Alan Marechal, Jean Marie Filhol, Yannick Valogne, Julien Valton, Aymeric Duclert, Philippe Duchateau and Laurent Poirot)
