Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing
J Li, NJ Stagg, J Johnston, MJ Harris, SA Menzies… - Cancer cell, 2017 - cell.com
J Li, NJ Stagg, J Johnston, MJ Harris, SA Menzies, D DiCara, V Clark, M Hristopoulos…
Cancer cell, 2017•cell.comSummary 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 …
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 …
Summary
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.
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