Taken together, these trial results reveal that the core challenges impeding current CAR-T therapy for brain tumors include susceptibility to antigen escape with single-target approaches, such as loss of EGFRvIII, and an immunosuppressive TME (e.g., upregulation of PD-L1/IDO1), and insufficient CAR-T cell persistence. The gene discussed is CD274; the disease is brain neoplasm.