Clinical Development and Therapeutic Applications of Bispecific Antibodies for Hematologic Malignancies.

Abstract

Bispecific antibodies are composed of two monoclonal antibodies that engage T cells with tumor cell antigens and lead to tumor cell lysis. The most common types fall into the category of bispecific T cell engagers, or BiTEs, that have the canonical CD3-CD19 bispecific construct. Blinatumomab is the first bispecific antibody that received FDA approval for relapsed refractory B cell precursor acute lymphoblastic leukemia. Blinatumomab has been shown to have robust clinical outcomes and is associated with adverse events such as cytokine release syndrome and neurotoxicity. Other bispecific antibodies are under clinical investigation for multiple myeloma and acute myeloid leukemia. Along with immune checkpoint inhibitors and chimeric antigen T cell receptor therapies, bispecific antibodies are considered a mainstay as a therapeutic option for cancer immunotherapies for Hematologic malignancies.