CD19 and CD22 CAR-T(Yake Biotechnology)

The prognosis of relapsed acute lymphoblastic leukemia (ALL) after allogeneic transplantation is dismal when treated with conventional approaches. While single‐target CD19 or CD22 chimeric antigen receptor (CAR) T‐cell therapy has achieved high complete remission (CR) rates in refractory/relapsed B‐ALL, it could not maintain a durable remission in most patients. To prolong relapse‐free survival, we sequentially combined CD19 and CD22 CAR‐T cells to treat post‐transplant relapsed B‐ALL patients with both CD19/CD22 antigen expression on lymphoblasts. Patient‐derived donor cells were collected to produce CAR‐T cells that were transfected by lentiviral vectors encoding second generation CARs composed of CD3ζ and 4–1BB. The second T‐cell infusion was scheduled at least 1 month, and usually within 6 months after the first CAR‐T treatment. Twenty‐seven adult and pediatric patients, including 11 (41%) with extramedullary diseases (EMD), received the first CD19 CAR‐T and 23 (85%) achieved CR. Subsequently, 21 out of 27 patients received the second CD22 CAR‐T and were followed‐up for a median of 19.7 (range, 5.6–27.3) months; 14 cases remained in CR, seven relapsed and two of them died from disease progression; Kaplan–Meier survival analysis showed overall survival and event‐free survival rates of 88.5% and 67.5%, respectively, at both 12 months and 18 months. CAR‐T associated graft‐versus‐host disease (GVHD) occurred in 23% of patients, with 8% new‐onset acute GVHD and 15% persistent or worsened pre‐existing cGVHD before CAR‐T. This combination strategy of sequential CD19 and CD22 CAR‐T therapy significantly improved the long‐term survival in B‐ALL patients who relapsed after transplantation.