CD38 (tumor cells) x CD28 (T cells)

Class

Bispecific costimulatory antibody

Pathway

Costimulatory bispecific that engages CD28 on T cells while binding CD38 on myeloma cells, used to amplify T-cell activation in combination with a CD3-based T-cell engager (linvoseltamab)

This mechanism describes a costimulatory bispecific antibody designed to strengthen T-cell attacks against myeloma cells. Full T-cell activation typically requires two coordinated signals: an antigen-recognition signal delivered through the T-cell receptor complex (CD3), and a costimulatory signal, classically delivered when CD28 on the T-cell surface engages ligands on an antigen-presenting cell. Tumor cells frequently lack these costimulatory ligands, so when a separate CD3-based T-cell engager directs T cells toward the tumor, the resulting activation can be incomplete, leaving T cells prone to poor proliferation or early exhaustion. This bispecific addresses that gap by binding CD38, a surface protein abundant on myeloma cells, while simultaneously engaging CD28 on nearby T cells. This brings the missing costimulatory signal directly to the tumor microenvironment, delivered in the same physical location where the CD3-engager is providing antigen-recognition signaling. Used together, the two antibodies are intended to reconstitute a more complete, coordinated activation program in T cells specifically at the tumor site. This approach is relevant to multiple myeloma and other CD38-expressing malignancies, and more broadly illustrates a strategy for enhancing engineered T-cell therapies by supplying costimulation that tumors do not naturally provide.