CD19/CD22 bispecific chimeric antigen receptor‑NK‑92 cells are developed and evaluated

Abstract

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 complica‑ tions 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 cytom‑ etry. 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 demon‑ strate 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.