- Chimeric antigen receptor (CAR) T cell therapy has emerged as an exciting immunotherapy approach for cancer that does not require pre-existing anti-tumor immunity. CAR-T cells are autologous T anti-CD19 targeting chimeric antigen receptor (CAR)-T cells induce unprecedented durable remissions for many patients with chemotherapy-refractory B cell malignancies. Cytokine release syndrome (CRS) which induced by CAR-T cells from rapid immune activation is the most significant toxicity. The clinical signs of CRS correlate with CAR-T cell activation. In the case of the abnormal activity, CAR-T cells need to be deactivated quickly.
- Y-inducible X domain technology enables the degradation of CAR protein within 30 min by the addition of Y small molecule for CAR-T inactivation. For degradation, ubiquitin ligase complex is activated through the interaction of Y small molecule with CAR. Y small molecule induces to interact between CAR and ubiquitin ligase complex. After binding ubiquitin ligase complex, CAR is degraded quickly and then inactivated.