Researchers have developed a T cell dependent bispecific antibody that can potentially be used in treating multiple myeloma and other B cell malignances.
Multiple myeloma, a malignancy of plasma cells, is an incurable disease with high mortality rate and median survival of less than 5 years. It is characterized by dysregulated growth of abnormal plasma cells in the bone marrow and overproduction of intact monoclonal antibodies that eventually lead to clinical manifestations including anemia, renal failure, hypercalcemia and skeletal lesions. The disease is currently treated using combinations of proteasome inhibitors, immunomodulators, and corticosteroids, with bone marrow transplantation as an additional option for eligible patients. Current clinical trials for treating multiple myeloma include monoclonal antibodies targeting CD38 (daratumomab) and SLAMF7 (elotuzumab).
A study published in the Immunity journal described how CD3-bispecific antibody induces intracellular T cell signaling and shows that the dimensions of the target molecule and epitope location play a key role in the efficiency of the synapse formation and subsequent T cell activation. The findings lead to the development of an anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) that targets the B cell lineage marker FcRH5 expressed in multiple myeloma tumour cells.
FcRH5 (also known as FcRL5, IRTA2, or CD307) has been identified as an attractive B cell line- age-specific surface marker in myeloma as its expression has been detected as early as pre-B cells and retained in plasma cells. The study found that the anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys.
The findings suggest that the anti-FcRH5/CD3 TDB has the potential in treating multiple myeloma and other B cell malignancies.