Allogeneic CD19 CAR T with anti-rejection CD70 CAR to overcome antigen escape and evade alloimmune responses: in vivo study

CAR T cells can achieve sustained clinical benefit in B cell malignancies. Despite the many potential advantages over autologous products, allogeneic CAR T cells carry a higher risk of rejection, which may limit persistence and therapeutic efficacy. Researchers at Allogene Therapeutics Inc., South San Francisco, CA designed an optimized CD70 CAR that prevents rejection of allogeneic CAR T cells by targeting activated alloreactive lymphocytes. Co-expression of this CD70 CAR with a CD19 CAR resulted in sustained CAR T cell persistence in the presence of alloreactive lymphocytes and prolonged antitumor activity in a CD19 antigen escape model. In vivo, CD19/CD70 dual CAR T cells eliminated B cells and CD70⁺ T cells derived from patients with systemic lupus erythematosus in humanized mouse models, resulting in reduced immunoglobuline production. The authors conclude that an allogeneic CD19/CD70 dual CAR T cell therapy may broaden clinical applicability while enabling the use of less intensive lymphodepleting conditioning regimens prior to CAR T cell infusion.