CD38 and CD28 (myeloma cells) x CD3 and CD28 (T cells)

Class

Trispecific/tetraspecific costimulatory T-cell engaging antibody

Pathway

Anti-CD38/CD3xCD28 trispecific antibody that co-targets CD38 and CD28 on myeloma cells while co-stimulating CD3 and CD28 on T cells, intended to enhance T-cell cytotoxicity, stimulate memory/effector T-cell proliferation, and reduce regulatory T cells

CD38 is a surface protein expressed at high density on malignant plasma cells in multiple myeloma, and it has long served as a target for antibody-based treatment of this disease. This mechanism uses an engineered antibody format with several binding arms, so that it simultaneously engages CD38 on myeloma cells, CD3 (the core signaling component of the T-cell receptor complex) on T cells, and CD28 on both cell types. By physically bridging a myeloma cell to a T cell through CD38 and CD3, the antibody redirects the T cell to recognize and destroy the tumor cell, independent of the T cell's original antigen specificity. CD3 engagement alone delivers only a partial activation signal; adding CD28 costimulation directly at the point of contact between tumor and T cell supplies a second signal that more completely activates the T cell, supports its proliferation and survival, favors expansion of memory and effector T-cell populations, and works against regulatory T cells that would otherwise dampen anti-tumor immunity. This layered signaling design is intended to produce more thorough and durable T-cell killing than antigen-CD3 engagement alone, which is especially relevant in myeloma, where prior treatment can leave the T-cell compartment depleted or functionally exhausted. The underlying principles draw on general T-cell biology applied broadly across engineered immunotherapies for blood cancers.