Anti-CD5 CAR-T cells with a tEGFR safety switch exhibit potent toxicity control
Haolong Lin, Jiali Cheng, Li Zhu, Yuhao Zeng, Zhenyu Dai, Yicheng Zhang, Xiaojian Zhu, Wei Mu
Abstract
The dire prognosis of relapsed or refractory (r/r) aggressive T-cell malignancies underscores an urgent need for improved therapeutic strategies [ 1 ]. The efficacy of chimeric antigen receptor (CAR) modified T-cell therapy has profoundly impacted the treatment landscape for hematologic malignancies. Its success in B cell and plasma cell tumors is gradually extending to T cell malignancies. Specifically, CAR-T cells targeting CD5 and CD7, has shown promise in treating T-cell malignancies [ 2 , 3 ]. However, patients often suffer from adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), virus reactivation, and T-cell aplasia post-CAR-T cell infusion [ 4 , 5 , 6 ]. These complications present substantial challenges to the wider application of CAR-T cell therapy in T-cell malignancies, necessitating the development of safety switch systems to attenuate potentially life-threatening side effects and to restore immune function after tumor elimination.