A phase I trial evaluated the safety and efficacy of CD22-CAR T cells in 21 patients with relapsed or refractory B-ALL, including 17 who had previously received CD19-directed immunotherapy. CD22-CAR T cells showed potent anti-leukemic activity, with 73% of patients (11/15) achieving complete remission at doses of ≥1×10⁶ CD22-CAR T cells/kg. Median remission duration was 6 months, and 5/5 patients with CD19dim/neg B-ALL achieved remission. Relapses were associated with reduced CD22 site density, which may allow escape from CD22-CAR T cells. These results demonstrate that CD22-CAR T cells can achieve comparable potency to CD19-CAR T cells in B-ALL, even in cases resistant to CD19-targeted immunotherapy. The CD22-CAR T cells showed robust expansion and persistence, with detectable cells in peripheral blood, bone marrow, and cerebrospinal fluid. Toxicity was primarily cytokine release syndrome (CRS), with grade 3 CRS observed in one patient. The CD22-CAR T cells demonstrated strong anti-leukemic activity, with 12 patients achieving complete remission (CR), including 9 with MRD-negative status. CD22-CAR T cells were effective even in patients with CD19-negative or dim B-ALL. Relapse was associated with reduced CD22 site density, but not with CD22 mutations or changes in mRNA levels. The study also demonstrated that CD22-CAR T cells can be used in patients who had previously received CD19-based immunotherapy. The CD22-CAR T cells showed robust expansion and persistence, with detectable cells in peripheral blood, bone marrow, and cerebrospinal fluid. The study highlights the importance of antigen density in regulating CAR function. The CD22-CAR T cells were well-tolerated, with no severe neurotoxicity or seizures. The results suggest that CD22-CAR T cells can be an effective alternative to CD19-CAR T cells in B-ALL, particularly in cases where CD19 expression is lost or reduced. The study also demonstrated that CD22-CAR T cells can be used in combination with CD19-CAR T cells to target multiple antigens, potentially overcoming resistance to immunotherapy. The study provides evidence that CD22 is a viable target for CAR T cell therapy in B-ALL, and that CD22-CAR T cells can achieve comparable efficacy to CD19-CAR T cells. The study also highlights the importance of antigen density in regulating CAR function. The CD22-CAR T cells showed robust expansion and persistence, with detectable cells in peripheral blood, bone marrow, and cerebroA phase I trial evaluated the safety and efficacy of CD22-CAR T cells in 21 patients with relapsed or refractory B-ALL, including 17 who had previously received CD19-directed immunotherapy. CD22-CAR T cells showed potent anti-leukemic activity, with 73% of patients (11/15) achieving complete remission at doses of ≥1×10⁶ CD22-CAR T cells/kg. Median remission duration was 6 months, and 5/5 patients with CD19dim/neg B-ALL achieved remission. Relapses were associated with reduced CD22 site density, which may allow escape from CD22-CAR T cells. These results demonstrate that CD22-CAR T cells can achieve comparable potency to CD19-CAR T cells in B-ALL, even in cases resistant to CD19-targeted immunotherapy. The CD22-CAR T cells showed robust expansion and persistence, with detectable cells in peripheral blood, bone marrow, and cerebrospinal fluid. Toxicity was primarily cytokine release syndrome (CRS), with grade 3 CRS observed in one patient. The CD22-CAR T cells demonstrated strong anti-leukemic activity, with 12 patients achieving complete remission (CR), including 9 with MRD-negative status. CD22-CAR T cells were effective even in patients with CD19-negative or dim B-ALL. Relapse was associated with reduced CD22 site density, but not with CD22 mutations or changes in mRNA levels. The study also demonstrated that CD22-CAR T cells can be used in patients who had previously received CD19-based immunotherapy. The CD22-CAR T cells showed robust expansion and persistence, with detectable cells in peripheral blood, bone marrow, and cerebrospinal fluid. The study highlights the importance of antigen density in regulating CAR function. The CD22-CAR T cells were well-tolerated, with no severe neurotoxicity or seizures. The results suggest that CD22-CAR T cells can be an effective alternative to CD19-CAR T cells in B-ALL, particularly in cases where CD19 expression is lost or reduced. The study also demonstrated that CD22-CAR T cells can be used in combination with CD19-CAR T cells to target multiple antigens, potentially overcoming resistance to immunotherapy. The study provides evidence that CD22 is a viable target for CAR T cell therapy in B-ALL, and that CD22-CAR T cells can achieve comparable efficacy to CD19-CAR T cells. The study also highlights the importance of antigen density in regulating CAR function. The CD22-CAR T cells showed robust expansion and persistence, with detectable cells in peripheral blood, bone marrow, and cerebro