Date: 2016-01-11
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in Scientific Reports
Company: Cellectis (France)
Product: CAR architecture
Action
mechanism: cell therapy/immunotherapy product/gene therapy
Disease:
Therapeutic area:
Country:
Trial details:
Latest
news: * On January 11, 2016, Cellectis announced the publication of a study in Scientific Reports, a Nature Publishing Group journal, describing the design and development of a new CAR architecture with an integrated switch-on system that permits control over CAR T-cell functions. This integrated switch-on system offers the advantages of controllable CAR T-cells for safety while allowing for the possibility of multiple cytotoxicity cycles using a small molecule drug.
The possibility to control spatially and temporally the CAR T activity is very desirable to mitigate potential unwanted risks, such as cytokine-release syndrome (CRS) and the “on- 1 target, off-tumor” effect . To date, few strategies are available and mostly rely on suicide mechanisms that ultimately lead to a complete eradication of the engineered T-cells, thus resulting in a premature end of the treatment. Consequently, implementing non-lethal, spatiotemporal control of gene edited CAR T-cells represents an important advancement in improving the CAR T-cell technology.
In this report, Alexandre Juillerat, Ph.D., and his collaborators engineered a system directly integrated within the CAR architecture. In particular, they showed that such system turns a CAR T-cell from an off-state to an on-state upon addition of a small molecule, inducing the cytolytic properties of the gene edited T-cell. Overall, this non-lethal system not only offers the advantage of a temporal control of activation to mitigate the risk of CAR-induced toxicities
but also enables opportunities for spatial activation of the engineered CAR T-cells using local targeted drug delivery.
