Modulation of chimeric antigen receptor surface expression by a small molecule switch

Modulation of chimeric antigen receptor surface expression by a small molecule switch

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Abstract Background Engineered therapeutic cells have attracted a great deal of interest due to their potential applications in treating a wide range of diseases, including cancer Physical Inactivity, Non-Communicable Diseases and National Fitness Plan of China for Physical Activity and autoimmunity.Chimeric antigen receptor (CAR) T-cells are designed to detect and kill tumor cells that present a specific, predefined antigen.The rapid expansion of targeted antigen beyond CD19, has highlighted new challenges, such as autoactivation and T-cell fratricide, that could impact the capacity to manufacture engineered CAR T-cells.Therefore, the development of strategies to control CAR expression at the surface of T-cells and their functions is under intense investigations.Results Here, we report the development and evaluation of an off-switch directly embedded within a CAR construct (SWIFF-CAR).

The incorporation of a self-cleaving degradation moiety controlled by a protease/protease inhibitor pair allowed Feline Stool-Associated Circular DNA Virus (FeSCV) in Diarrheic Cats in China the ex vivo tight and reversible control of the CAR surface presentation and the subsequent CAR-induced signaling and cytolytic functions of the engineered T-cells using the cell permeable Asunaprevir (ASN) small molecule.Conclusions The strategy described in this study could, in principle, be broadly adapted to CAR T-cells development to circumvent some of the possible hurdle of CAR T-cell manufacturing.This system essentially creates a CAR T-cell with an integrated functional rheostat.