CD47/SIRPα blocking enhances CD19/CD3-bispecific T cell engager antibody-mediated lysis of B cell malignancies.

T cell immunotherapies are promising options in leukemia, among which the CD19/CD3-bispecific T cell engager antibody blinatumomab (MT103) has shown high response rates at very low doses in patients with lymphoma. However, the high CD47 expression in human lymphoma cells has limited the curative effects of blinatumomab other antibodies. Here we report the combined use of blinatumomab with a CD47-blocking antibody. CD47 antibodies preferentially enabled phagocytosis of non-Hodgkin lymphoma cells by both human and murine macrophages. Treatment of human non-Hodgkin lymphoma cell-engrafted mice with CD47 antibody and blinatumomab separately inhibited lymphoma partially, while combination treatment led to persistent control of lymphoma. These antibodies enhanced the therapeutic efficacy through mechanisms combining both innate and adaptive immune responses by induction of phagocytosis and T cell cytotoxicity. The combination strategy in this study might be applicable to many other cancers.