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

Related Articles

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

Cancer Cell. 2017 Mar 13;31(3):383-395

Authors: Li J, Stagg NJ, Johnston J, Harris MJ, Menzies SA, DiCara D, Clark V, Hristopoulos M, Cook R, Slaga D, Nakamura R, McCarty L, Sukumaran S, Luis E, Ye Z, Wu TD, Sumiyoshi T, Danilenko D, Lee GY, Totpal K, Ellerman D, Hötzel I, James JR, Junttila TT

Abstract
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.

PMID: 28262555 [PubMed - indexed for MEDLINE]

http://ift.tt/2t0YC3L