Anti-CD19/CD22 CAR-T cells(Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine)

Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19 Chimeric Antigen Receptor T-cells (CAR-Ts) therapies have been approved for these patients. Dual-target CAR-Ts against CD19 and CD22 have recently been developed to improve the efficacy of the single-target therapy; however, extent of the improvement using this dual-target therapy has yet to be determined. We performed a meta-analysis of the outcome and safety of CAR-Ts, comparing anti-CD19 vs anti-CD22 vs dual-target anti-CD19/CD22 CAR-Ts, to elucidate the differences and limitations of these therapies in adult patients with R/R B-ALL. Although the limitations of our study derived from heterogeneity in the included publications, our results suggest that anti-CD19/CD22 CAR-Ts generate lower incidence of relapse and neurotoxicity, but similar results were obtained regarding complete remission, minimal residual disease, overall survival, and cytokine release syndrome compared with single-target anti-CD19 and anti-CD22 CAR-Ts.

Anti-CD19 chimeric antigen receptor (CAR)-T cells have improved the outcomes of patients with B cell leukemia and lymphoma. However, their applications and positive outcomes remain limited. CAR-T cells are currently restricted to autologous blood as their source and their use can lead to downregulation of CD19 expression along with complications such as graft-versus-host disease and cytokine release syndrome. The present study aimed to develop anti-CD19/CD22 bispecific CAR structures using an anti-CD22 monoclonal antibody clone from chickens and analyze them in natural killer (NK)-92 cells, a human NK cell line, in vitro and in vivo. Anti-CD19/CD22 CAR-NK-92 cell cytotoxicity was assessed by the survival of target cells and counted using flow cytometry. Anti-CD22/CD19 and loop-structured anti-CD19/CD22 bi-specific CAR-NK-92 cells showed improved efficacy against OCI-Ly7 cells, a human B cell lymphoma cell line, compared with other CAR structures. These results demonstrate the potential of anti-CD19/CD22 bispecific CAR-NK cells and suggested that optimizing CAR structures in NK cells can improve the efficacy of CAR therapy.