CELL INTELLIGENCE · 肿瘤细胞治疗研究

The worldwide use of CD19 chimeric antigen receptor (CAR)-T cells has increased the response rate in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Clinical practice has become much safer with the help of immunotherapy-related toxicity management guidelines, such as the ASTCT consensus grading system. Tocilizumab and steroids are the major interventions for controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). New drugs and interventions for uncontrolled CRS and ICANS, including JAK1/2 inhibitors, have also been investigated. The combination of ruxolitinib and steroids effectively controlled severe CRS without impeding CAR-T cell expansion. Patients with refractory CNS3 status and CNS masses were excluded from the clinical trials because of the high risk of severe ICANS. Intracranial injections of steroids and Ommaya capsule implantation were effective. For some heavily treated patients, the difficulties in CAR-T cell manufacturing and expansion may be resolved by combination with blinatumumab. Relapse is a major concern after CAR-T therapy, and combination interventions, such as allogeneic stem cell transplantation, dual-target CAR-T cell therapies, and sequential CD19/22 CAR-T infusion, have been investigated in many centers. For T-lineage-targeted CAR-T therapies, the CAR T-cell fratricide can be overcome using many techniques. The efficacy and safety of CD7+ CAR-T cell therapy have been widely reported in recent years. A high response rate can be achieved when the immune reconstitution is prolonged. Infections, particularly viral reactivations, should be carefully monitored, as relapses are another potential issue. Switching targets and eliminating residual CD7+ CAR-T cells in the blood are key points for patients who relapse after CD7+ CAR-T cell therapy. CAR-T cell therapies for AML have not been investigated in a large-scale cohort, except for CD19-positive AML with the AML1-ETO fusion gene.