Anti-CD22 CAR-T Cells

For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion...No treatment-related death occurred. The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.

P2, N=100, Recruiting, Beijing Boren Hospital | Trial completion date: Oct 2022 --> Oct 2024 | Trial primary completion date: May 2022 --> May 2024

We previously confirmed that sequential infusions of CD20 and CD22 CAR-T cells significantly improved the prognosis of the B-NHL patients, while some advanced patients still progressed to death during these CAR-T cell treatments...Disease progression was observed in both patients after primary CAR-T cell infusion but robust re-expansion of prior CAR-T cells and anti-tumor effects was induced by infusion of a secondary CAR-T cells. These results indicate sequential infusions of CAR-T cells with a short interval may improve therapeutic efficacy in the B-NHL patients by promoting expansion of prior CAR-T cells.

The ASCT combined with CD19, CD20 or CD22 CAR T-cell therapy would be then administered to patients whose stem cells were successfully collected or had been already prepared...In comparison, in the group of ASCT combined with CAR T-cells therapy, patients in remission had longer PFS (11 months vs 4 months, P=0.02), with no significant difference in the overall survival length between the two groups ( 11 months vs 9 months, P =0.52). Conclusion 1.The CAR T-cell therapy could augment its efficacy in treatment of advanced R/RCNSBL.2.The neurotoxicity of CAR T- cells therapy could be mitigated, and there was no death related to treatment.3.The combined treatment of ASCT and CAR T-cell therapy could increase sustained response and longer survival length.

All patients accepted fludarabine and/or cyclophosphamide before infusion. Among 4 NR patients, 3 died of disease progression, and 1 accepted salvage transplantation who had survived for 4.6 months. Conclusion CD22 CAR T-cells was highly effective in inducing remission in adult r/r B-ALL patients,transplantation followed-by CD22-CART allowed CR patients to obtain a remission of 4-39.7months.

Conditioning with busulfan, fludarabine-based regimen combined with allo-CD19/CD22 CAR-T was applied. Tacrolimus, mycophenolate mofetil, a short-term methotrexate and antithymocyte globulin were used for graft-versus-host disease (GVHD) prophylaxis...CAR-T cells still exist persistently post-transplant in majority of patients, which may contribute a long-term anti-lymphoma effect. With current protocol, no aGVHD was observed, viral reactivation was mild and encouraging disease control was found. Haplo-HSCT with conditioning including allo-CD19/CD22 CAR-T cells is a safe and effective strategy for r/r B-NHL. Long-term follow-up is needed.

CD19 and CD22 CAR T cells were infused with a median interval of 1.7 (range, 1.1 to 5.2) months...Conclusion Sequential CD19-22 CAR T cell therapy can achieve promising long-term outcome with a 2-year LFS of 60% in pediatric patient with r/r B-ALL without post-CAR transplantation. Early Ig recovery has high risk of relapse.