Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing

作者：Li Ji; Stagg Nicola J; Johnston Jennifer; Harris Michael J; Menzies Sam A; DiCara Danielle; Clark Vanessa; Hristopoulos Maria; Cook Ryan; Slaga Dionysos; Nakamura Rin; McCarty Luke; Sukumaran Siddharth; Luis Elizabeth; Ye Zhengmao; Wu Thomas D; Sumiyoshi Teiko; Danilenko Dimitry; Lee Genee Y; Totpal Klara; Ellerman Diego; Tzel Isidro Ho; James John R; Junttila Teemu T^*

来源：Cancer Cell, 2017, 31(3): 383-395.

DOI：10.1016/j.ccell.2017.02.001

The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. 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. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.

• 出版日期2017-3-13