Joseph Mikhael, MD, spoke about the mechanism of action of bispecific antibody teclistamab relative to other agents in the space such monoclonal antibodies and CAR T-cell therapies in multiple myeloma.
In an interview with CancerNetwork®, Joseph Mikhael, MD, professor of Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope; chief medical officer at the International Myeloma Foundation; and American Society of Hematology expert, discussed the mechanism of action of teclistamab as a treatment for patients with multiple myeloma. In particular, he discusses the agent’s potential to induce T-cell destruction of myeloma cells.
Teclistamab is one of many bispecific antibody agents that are being developed in multiple myeloma. Bispecifics [can focus on] 2 different targets. Historically, monoclonal antibodies have had a sole target on the myeloma surface like CD38 or BCMA [B-cell maturation antigen]. The concept here is that 1 of the 2 arms would hinge to the myeloma cell in the form of teclistamab, targeting BCMA on the myeloma cell, which we know is prolifically expressed in myeloma, even in heavily relapsed disease. The other arm is designed to attach to the CD3 antigen on a T cell. In doing so, it engages that T cell, activates it, and activates the pathway that should then downstream activate more T cells to directly engage it to destroy the myeloma. It is much of the same concept that we have in CAR T cell therapy, but right off the shelf directly to the patient without the need to pre-collect T cells in advance. We can give this direct bispecific antibody that connects the T cell to the myeloma cell and hopefully invoke T cell destruction and other immune mechanisms of destruction of the myeloma cell.