BiTE: a new class of antibodies that recruit T-cells

Certain bispecific antibodies hold promise for redirecting cytotoxic T-cells, the body's most effective killer cells, against malignant cells. This cannot be achieved by conventional monoclonal antibodies because T-cells do not express antibody-binding Flay receptors. Many bispecific antibody formats have been developed over the past 20 years that bind with one arm to an activating surface receptor on T-cells and with the other arm to a tumor-associated antigen, but only a few have made it into clinical trials. This article reviews a novel class of bispecific antibodies, known as BiTE antibodies, in terms of their mode of action, in vitro and in vivo characteristics and clinical activity. It appears that BiTE antibodies have overcome many of the issues of previous bispecific antibody formats regarding the need for T-cell pre- or co-stimulation, low potency of redirected lysis, or nonconditional T-cell activation. Monotherapy with a BiTE antibody directed against CD19 has provided impressive results in the treatment of refractory non-Hodgkin's lymphoma (NHL) patients, showing depletion of peripheral B lymphoma cells, confirmed partial and complete responses, clearance of bone marrow from tumor cells and reduction of splenomegaly. We describe how BiTE antibodies are evolving into a new class of antibody-based therapeutics, with several new members in various stages of preclinical development.